Genetic Variant NM_015407.5:c.379G>T (chr3-51978356-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015407.5(ABHD14A):c.379G>T(p.Val127Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

ABHD14A
NM_015407.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.31

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21608663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABHD14A	NM_015407.5 link	c.379G>T	p.Val127Leu	missense_variant	Exon 3 of 5	ENST00000273596.8	NP_056222.2	Q9BUJ0
ABHD14A-ACY1	NM_001316331.2 link	c.234G>T	p.Pro78Pro	synonymous_variant	Exon 3 of 17		NP_001303260.1	B4DNW0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABHD14A	ENST00000273596.8 link	c.379G>T	p.Val127Leu	missense_variant	Exon 3 of 5	1	NM_015407.5	ENSP00000273596.3		Q9BUJ0
ABHD14A-ACY1	ENST00000463937.1 link	c.379G>T	p.Val127Leu	missense_variant	Exon 3 of 16	5		ENSP00000420487.1		C9JMV9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1399232

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690112

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

.;.;.;T;.

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.76

LIST_S2

Pathogenic

0.99

D;D;D;D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.22

T;T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.85

.;.;.;L;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.1

N;N;.;N;N

REVEL

Benign

0.080

Sift

Benign

0.086

T;T;.;T;D

Sift4G

Benign

0.090

T;T;T;T;D

Polyphen

0.47, 0.86

.;.;.;P;P

Vest4

0.29, 0.36, 0.11

MutPred

0.46

.;.;.;Gain of helix (P = 0.027);Gain of helix (P = 0.027);

MVP

0.53

MPC

0.46, 0.49

ClinPred

0.87

GERP RS

4.7

Varity_R

0.097

gMVP

0.55

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over