Variant 3-157265531-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001167912.2(VEPH1):c.2260A>C(p.Lys754Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

VEPH1
NM_001167912.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.86

Variant links:

Genes affected

VEPH1 (HGNC:25735): (ventricular zone expressed PH domain containing 1) Predicted to enable phosphatidylinositol-5-phosphate binding activity. Involved in negative regulation of SMAD protein signal transduction and negative regulation of transforming growth factor beta receptor signaling pathway. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

VEPH1 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39956415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VEPH1	NM_001167912.2 linkuse as main transcript	c.2260A>C	p.Lys754Gln	missense_variant	13/14	ENST00000362010.7
LOC101928236	XR_007096141.1 linkuse as main transcript	n.1708-17693T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VEPH1	ENST00000362010.7 linkuse as main transcript	c.2260A>C	p.Lys754Gln	missense_variant	13/14	1	NM_001167912.2	P1	Q14D04-1
	ENST00000487238.5 linkuse as main transcript	n.331+25732T>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459994

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726274

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

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

Sep 12, 2023

The c.2260A>C (p.K754Q) alteration is located in exon 13 (coding exon 12) of the VEPH1 gene. This alteration results from a A to C substitution at nucleotide position 2260, causing the lysine (K) at amino acid position 754 to be replaced by a glutamine (Q). 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

Uncertain

0.42

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

.;T;T

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.90

D;.;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.40

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

.;L;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.6

N;N;N

REVEL

Uncertain

0.30

Sift

Benign

0.068

T;T;T

Sift4G

Benign

0.14

T;D;D

Polyphen

1.0

D;D;D

Vest4

0.47

MutPred

0.46

.;Loss of ubiquitination at K754 (P = 0.013);Loss of ubiquitination at K754 (P = 0.013);

MVP

0.52

MPC

0.29

ClinPred

0.93

GERP RS

5.5

Varity_R

0.29

gMVP

0.41

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