Variant rs323893 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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:3

Conservation

PhyloP100: -2.33

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=-0.88).

BP6

Variant 3-51986395-C-T is Benign according to our data. Variant chr3-51986395-C-T is described in ClinVar 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/exons	MANE	UniProt
ACY1	NM_000666.3 linkuse as main transcript	c.437-20C>T		intron_variant		ENST00000636358.2
ABHD14A-ACY1	NM_001316331.2 linkuse as main transcript	c.707-20C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACY1	ENST00000636358.2 linkuse as main transcript	c.437-20C>T		intron_variant		1	NM_000666.3	P1	Q03154-1

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

GnomAD3 exomes

AF:

0.0513

AC:

12145

AN:

236718

Hom.:

969

AF XY:

0.0472

AC XY:

6049

AN XY:

128158

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 SAS exome

AF:

0.0654

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

Gnomad4 AFR exome

AF:

0.325

Gnomad4 AMR exome

AF:

0.0313

Gnomad4 ASJ exome

AF:

0.0270

Gnomad4 EAS exome

AF:

0.0742

Gnomad4 SAS exome

AF:

0.0627

Gnomad4 FIN exome

AF:

0.0188

Gnomad4 NFE exome

AF:

0.0182

Gnomad4 OTH exome

AF:

0.0504

GnomAD4 genome

AF:

0.107

AC:

16331

AN:

151996

Hom.:

2159

Cov.:

AF XY:

0.105

AC XY:

7812

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.314

Gnomad4 AMR

AF:

0.0523

Gnomad4 ASJ

AF:

0.0231

Gnomad4 EAS

AF:

0.0699

Gnomad4 SAS

AF:

0.0673

Gnomad4 FIN

AF:

0.0164

Gnomad4 NFE

AF:

0.0207

Gnomad4 OTH

AF:

0.0934

Alfa

AF:

0.0662

Hom.:

251

Bravo

AF:

0.122

Asia WGS

AF:

0.110

AC:

384

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 26, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 27, 2020	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.023

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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