rs323895

chr3-51987300-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000666.3(ACY1):c.708-9A>G variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001557

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.88

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:):

ABHD14A-ACY1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
ACY1	NM_000666.3 linkuse as main transcript	c.708-9A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000636358.2
ABHD14A-ACY1	NM_001316331.2 linkuse as main transcript	c.978-9A>G		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACY1	ENST00000636358.2 linkuse as main transcript	c.708-9A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000666.3	P1	Q03154-1

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

GnomAD3 exomes

AF:

0.0512

AC:

12863

AN:

250992

Hom.:

1039

AF XY:

0.0470

AC XY:

6378

AN XY:

135666

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 SAS exome

AF:

0.0653

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

Gnomad4 AFR exome

AF:

0.320

Gnomad4 AMR exome

AF:

0.0312

Gnomad4 ASJ exome

AF:

0.0271

Gnomad4 EAS exome

AF:

0.0747

Gnomad4 SAS exome

AF:

0.0627

Gnomad4 FIN exome

AF:

0.0186

Gnomad4 NFE exome

AF:

0.0183

Gnomad4 OTH exome

AF:

0.0502

GnomAD4 genome

AF:

0.107

AC:

16317

AN:

152178

Hom.:

2141

Cov.:

AF XY:

0.105

AC XY:

7814

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.311

Gnomad4 AMR

AF:

0.0524

Gnomad4 ASJ

AF:

0.0231

Gnomad4 EAS

AF:

0.0720

Gnomad4 SAS

AF:

0.0679

Gnomad4 FIN

AF:

0.0166

Gnomad4 NFE

AF:

0.0208

Gnomad4 OTH

AF:

0.0938

Alfa

AF:

0.0424

Hom.:

659

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

Cadd

Benign

1.2

Dann

Benign

0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over