3-51986395-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000666.3(ACY1):c.437-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 1,607,980 control chromosomes in the GnomAD database, including 4,791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 2159 hom., cov: 32)

Exomes 𝑓: 0.032 ( 2632 hom. )

Consequence

ACY1
NM_000666.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.33

Publications

9 publications found

Variant links:

Genes affected

ACY1 (HGNC:177): (aminoacylase 1) This gene encodes a cytosolic, homodimeric, zinc-binding enzyme that catalyzes the hydrolysis of acylated L-amino acids to L-amino acids and an acyl group, and has been postulated to function in the catabolism and salvage of acylated amino acids. This gene is located on chromosome 3p21.1, a region reduced to homozygosity in small-cell lung cancer (SCLC), and its expression has been reported to be reduced or undetectable in SCLC cell lines and tumors. The amino acid sequence of human aminoacylase-1 is highly homologous to the porcine counterpart, and this enzyme is the first member of a new family of zinc-binding enzymes. Mutations in this gene cause aminoacylase-1 deficiency, a metabolic disorder characterized by central nervous system defects and increased urinary excretion of N-acetylated amino acids. Alternative splicing of this gene results in multiple transcript variants. Read-through transcription also exists between this gene and the upstream ABHD14A (abhydrolase domain containing 14A) gene, as represented in GeneID:100526760. A related pseudogene has been identified on chromosome 18. [provided by RefSeq, Nov 2010]

ACY1 links:

ABHD14A-ACY1 (HGNC:38856): (ABHD14A-ACY1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring abhydrolase domain containing 14A (ABHD14A) and aminoacylase 1 (ACY1) genes on chromosome 3. The read-through transcript encodes a protein that shares sequence identity with the downstream gene product but its N-terminal region is distinct due to the use of an alternate start codon relative to the upstream gene. [provided by RefSeq, Oct 2015]

ABHD14A-ACY1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 3-51986395-C-T is Benign according to our data. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51986395-C-T is described in CliVar as Benign. Clinvar id is 256754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACY1	NM_000666.3 link	c.437-20C>T		intron_variant	Intron 6 of 14	ENST00000636358.2	NP_000657.1	Q03154-1V9HWA0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACY1	ENST00000636358.2 link	c.437-20C>T		intron_variant	Intron 6 of 14	1	NM_000666.3	ENSP00000490149.1		Q03154-1
ABHD14A-ACY1	ENST00000463937.1 link	c.740-20C>T		intron_variant	Intron 7 of 15	5		ENSP00000420487.1		C9JMV9

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16259

AN:

151878

Hom.:

2135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.313

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0524

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.0703

Gnomad SAS

AF:

0.0675

Gnomad FIN

AF:

0.0164

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0207

Gnomad OTH

AF:

0.0920

GnomAD2 exomes

AF:

0.0513

AC:

12145

AN:

236718

AF XY:

0.0472

show subpopulations

Gnomad AFR exome

AF:

0.320

Gnomad AMR exome

AF:

0.0272

Gnomad ASJ exome

AF:

0.0277

Gnomad EAS exome

AF:

0.0768

Gnomad FIN exome

AF:

0.0198

Gnomad NFE exome

AF:

0.0217

Gnomad OTH exome

AF:

0.0427

GnomAD4 exome

AF:

0.0315

AC:

45875

AN:

1455984

Hom.:

2632

Cov.:

AF XY:

0.0315

AC XY:

22773

AN XY:

723778

show subpopulations

African (AFR)

AF:

0.325

AC:

10842

AN:

33342

American (AMR)

AF:

0.0313

AC:

1369

AN:

43772

Ashkenazi Jewish (ASJ)

AF:

0.0270

AC:

701

AN:

25968

East Asian (EAS)

AF:

0.0742

AC:

2935

AN:

39562

South Asian (SAS)

AF:

0.0627

AC:

5357

AN:

85426

European-Finnish (FIN)

AF:

0.0188

AC:

995

AN:

52984

Middle Eastern (MID)

AF:

0.0837

AC:

474

AN:

5660

European-Non Finnish (NFE)

AF:

0.0182

AC:

20172

AN:

1109106

Other (OTH)

AF:

0.0504

AC:

3030

AN:

60164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

2570

5140

7711

10281

12851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

948

1896

2844

3792

4740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.107

AC:

16331

AN:

151996

Hom.:

2159

Cov.:

AF XY:

0.105

AC XY:

7812

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.314

AC:

12945

AN:

41288

American (AMR)

AF:

0.0523

AC:

800

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0231

AC:

AN:

3470

East Asian (EAS)

AF:

0.0699

AC:

361

AN:

5166

South Asian (SAS)

AF:

0.0673

AC:

325

AN:

4826

European-Finnish (FIN)

AF:

0.0164

AC:

174

AN:

10624

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0207

AC:

1408

AN:

68014

Other (OTH)

AF:

0.0934

AC:

197

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

603

1206

1809

2412

3015

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0438

Hom.:

800

Bravo

AF:

0.122

Asia WGS

AF:

0.110

AC:

384

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 27, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.023

(source)

DANN

Benign

0.52

PhyloP100

-2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over