chr3-51987076-A-G

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.657+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 1,613,974 control chromosomes in the GnomAD database, including 3,298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 1511 hom., cov: 33)

Exomes 𝑓: 0.023 ( 1787 hom. )

Consequence

ACY1
NM_000666.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0400

Publications

4 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:

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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=-0.83).

BP6

Variant 3-51987076-A-G is Benign according to our data. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-51987076-A-G is described in CliVar as Benign. Clinvar id is 256756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACY1	NM_000666.3 link	c.657+15A>G		intron_variant	Intron 9 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.657+15A>G		intron_variant	Intron 9 of 14	1	NM_000666.3	ENSP00000490149.1		Q03154-1
ABHD14A-ACY1	ENST00000463937.1 link	c.960+15A>G		intron_variant	Intron 10 of 15	5		ENSP00000420487.1		C9JMV9

Frequencies

GnomAD3 genomes

AF:

0.0873

AC:

13280

AN:

152098

Hom.:

1488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0399

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.0721

Gnomad SAS

AF:

0.0397

Gnomad FIN

AF:

0.0162

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0135

Gnomad OTH

AF:

0.0761

GnomAD2 exomes

AF:

0.0400

AC:

10053

AN:

251432

AF XY:

0.0358

show subpopulations

Gnomad AFR exome

AF:

0.265

Gnomad AMR exome

AF:

0.0205

Gnomad ASJ exome

AF:

0.0224

Gnomad EAS exome

AF:

0.0770

Gnomad FIN exome

AF:

0.0190

Gnomad NFE exome

AF:

0.0141

Gnomad OTH exome

AF:

0.0322

GnomAD4 exome

AF:

0.0226

AC:

33093

AN:

1461758

Hom.:

1787

Cov.:

AF XY:

0.0223

AC XY:

16186

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.270

AC:

9033

AN:

33472

American (AMR)

AF:

0.0240

AC:

1074

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

587

AN:

26136

East Asian (EAS)

AF:

0.0746

AC:

2962

AN:

39700

South Asian (SAS)

AF:

0.0363

AC:

3131

AN:

86256

European-Finnish (FIN)

AF:

0.0182

AC:

970

AN:

53350

Middle Eastern (MID)

AF:

0.0718

AC:

411

AN:

5724

European-Non Finnish (NFE)

AF:

0.0112

AC:

12502

AN:

1112002

Other (OTH)

AF:

0.0401

AC:

2423

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

2161

4323

6484

8646

10807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

622

1244

1866

2488

3110

<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:

0.0877

AC:

13352

AN:

152216

Hom.:

1511

Cov.:

AF XY:

0.0858

AC XY:

6390

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.261

AC:

10844

AN:

41498

American (AMR)

AF:

0.0398

AC:

609

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

AN:

3472

East Asian (EAS)

AF:

0.0716

AC:

371

AN:

5178

South Asian (SAS)

AF:

0.0398

AC:

192

AN:

4828

European-Finnish (FIN)

AF:

0.0162

AC:

172

AN:

10626

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0135

AC:

920

AN:

67996

Other (OTH)

AF:

0.0777

AC:

164

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

523

1046

1568

2091

2614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<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:

0.0503

Hom.:

137

Bravo

AF:

0.0993

Asia WGS

AF:

0.0940

AC:

329

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.83

CADD

Benign

4.8

(source)

DANN

Benign

0.77

PhyloP100

-0.040

PromoterAI

-0.0075

Neutral

(source)

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