NM_000666.3:c.708-9A>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.708-9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0386 in 1,613,944 control chromosomes in the GnomAD database, including 4,738 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 2141 hom., cov: 33)

Exomes 𝑓: 0.031 ( 2597 hom. )

Consequence

ACY1
NM_000666.3 intron

Scores

Splicing: ADA: 0.00001557

Clinical Significance

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

Conservation

PhyloP100: -1.88

Publications

8 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=-0.89).

BP6

Variant 3-51987300-A-G is Benign according to our data. Variant chr3-51987300-A-G is described in ClinVar as Benign. ClinVar VariationId is 256757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACY1	NM_000666.3 link	c.708-9A>G		intron_variant	Intron 10 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.708-9A>G		intron_variant	Intron 10 of 14	1	NM_000666.3	ENSP00000490149.1		Q03154-1
ABHD14A-ACY1	ENST00000463937.1 link	c.1011-9A>G		intron_variant	Intron 11 of 15	5		ENSP00000420487.1		C9JMV9

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16245

AN:

152060

Hom.:

2117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.0525

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.0724

Gnomad SAS

AF:

0.0681

Gnomad FIN

AF:

0.0166

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0208

Gnomad OTH

AF:

0.0924

GnomAD2 exomes

AF:

0.0512

AC:

12863

AN:

250992

AF XY:

0.0470

show subpopulations

Gnomad AFR exome

AF:

0.315

Gnomad AMR exome

AF:

0.0271

Gnomad ASJ exome

AF:

0.0277

Gnomad EAS exome

AF:

0.0771

Gnomad FIN exome

AF:

0.0194

Gnomad NFE exome

AF:

0.0216

Gnomad OTH exome

AF:

0.0419

GnomAD4 exome

AF:

0.0315

AC:

46042

AN:

1461766

Hom.:

2597

Cov.:

AF XY:

0.0315

AC XY:

22895

AN XY:

727174

show subpopulations

African (AFR)

AF:

0.320

AC:

10702

AN:

33476

American (AMR)

AF:

0.0312

AC:

1397

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0271

AC:

707

AN:

26136

East Asian (EAS)

AF:

0.0747

AC:

2966

AN:

39700

South Asian (SAS)

AF:

0.0627

AC:

5411

AN:

86256

European-Finnish (FIN)

AF:

0.0186

AC:

993

AN:

53318

Middle Eastern (MID)

AF:

0.0850

AC:

490

AN:

5768

European-Non Finnish (NFE)

AF:

0.0183

AC:

20346

AN:

1111998

Other (OTH)

AF:

0.0502

AC:

3030

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

2760

5520

8279

11039

13799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

954

1908

2862

3816

4770

<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:

16317

AN:

152178

Hom.:

2141

Cov.:

AF XY:

0.105

AC XY:

7814

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.311

AC:

12904

AN:

41464

American (AMR)

AF:

0.0524

AC:

802

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0231

AC:

AN:

3470

East Asian (EAS)

AF:

0.0720

AC:

373

AN:

5178

South Asian (SAS)

AF:

0.0679

AC:

328

AN:

4828

European-Finnish (FIN)

AF:

0.0166

AC:

176

AN:

10620

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0208

AC:

1413

AN:

68002

Other (OTH)

AF:

0.0938

AC:

198

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

615

1230

1844

2459

3074

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:

0.0500

Hom.:

1051

Bravo

AF:

0.120

Asia WGS

AF:

0.110

AC:

384

AN:

3478

EpiCase

AF:

0.0238

EpiControl

AF:

0.0231

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

- -

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

-0.89

CADD

Benign

1.2

(source)

DANN

Benign

0.20

PhyloP100

-1.9

PromoterAI

-0.044

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.0

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