Variant 3-51975151-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015407.5(ABHD14A):c.16T>G(p.Cys6Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000176 in 1,136,558 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

ABHD14A
NM_015407.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.764

Variant links:

Genes affected

ABHD14A (HGNC:24538): (abhydrolase domain containing 14A) Predicted to enable hydrolase activity. Predicted to be integral component of membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ABHD14A 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:

ABHD14B (HGNC:28235): (abhydrolase domain containing 14B) Enables hydrolase activity. Involved in positive regulation of transcription by RNA polymerase II. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ABHD14B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0067032874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD14A	NM_015407.5 link	c.16T>G	p.Cys6Gly	missense_variant	1/5	ENST00000273596.8	NP_056222.2	Q9BUJ0
ABHD14A-ACY1	NM_001316331.2 link	c.-130T>G		5_prime_UTR_variant	1/17		NP_001303260.1	B4DNW0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD14A	ENST00000273596.8 link	c.16T>G	p.Cys6Gly	missense_variant	1/5	1	NM_015407.5	ENSP00000273596.3		Q9BUJ0
ABHD14A-ACY1	ENST00000463937.1 link	c.16T>G	p.Cys6Gly	missense_variant	1/16	5		ENSP00000420487.1		C9JMV9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000152

AC:

AN:

6578

Hom.:

AF XY:

0.00

AC XY:

AN XY:

3992

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000319

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000176

AC:

AN:

1136558

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

545706

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000105

Gnomad4 OTH exome

AF:

0.0000219

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000123

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 07, 2024

The c.16T>G (p.C6G) alteration is located in exon 1 (coding exon 1) of the ABHD14A gene. This alteration results from a T to G substitution at nucleotide position 16, causing the cysteine (C) at amino acid position 6 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0031

T;.;.;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.63

T;T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.0067

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.38

N;N;N;.

REVEL

Benign

0.034

Sift

Benign

0.080

T;T;D;.

Sift4G

Benign

0.11

T;T;T;.

Polyphen

0.018

B;.;B;.

Vest4

0.31

MutPred

0.47

Gain of disorder (P = 0.0049);Gain of disorder (P = 0.0049);Gain of disorder (P = 0.0049);Gain of disorder (P = 0.0049);

MVP

0.33

MPC

0.20

ClinPred

0.036

GERP RS

1.5

Varity_R

0.34

gMVP

0.26

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