chr3-51985385-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_000666.3(ACY1):c.184G>C(p.Val62Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,614,098 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000092 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 1 hom. )

Consequence

ACY1
NM_000666.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.55

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 made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13848028).

BP6

Variant 3-51985385-G-C is Benign according to our data. Variant chr3-51985385-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 975314.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACY1	NM_000666.3 link	c.184G>C	p.Val62Leu	missense_variant	Exon 4 of 15	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.184G>C	p.Val62Leu	missense_variant	Exon 4 of 15	1	NM_000666.3	ENSP00000490149.1		Q03154-1
ABHD14A-ACY1	ENST00000463937.1 link	c.487G>C	p.Val163Leu	missense_variant	Exon 5 of 16	5		ENSP00000420487.1		C9JMV9

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251342

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00473

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Intellectual disability

Benign:1

Jan 01, 2019

Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

.;.;.;T;.;.;T;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.93

D;D;D;.;D;D;D;D

M_CAP

Benign

0.059

MetaRNN

Benign

0.14

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.60

.;.;.;N;N;N;N;.

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.5

N;.;.;.;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.44

T;.;.;.;T;T;T;T

Sift4G

Benign

0.54

T;.;.;.;T;T;T;T

Polyphen

0.0010

.;.;.;B;.;.;B;.

Vest4

0.55

MVP

0.78

MPC

0.15

ClinPred

0.084

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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