Variant 3-157265575-C-T 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.2216G>A(p.Arg739His) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,613,314 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R739C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

VEPH1
NM_001167912.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.94

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:

Genome browser will be placed here

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=0.3498206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VEPH1	NM_001167912.2 linkuse as main transcript	c.2216G>A	p.Arg739His	missense_variant	13/14	ENST00000362010.7
LOC101928236	XR_007096141.1 linkuse as main transcript	n.1708-17649C>T		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.2216G>A	p.Arg739His	missense_variant	13/14	1	NM_001167912.2	P1	Q14D04-1
	ENST00000487238.5 linkuse as main transcript	n.331+25776C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251012

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461132

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

726832

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000480

Hom.:

Bravo

AF:

0.0000151

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000547

EpiControl

AF:

0.0000595

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

Feb 17, 2023

The c.2216G>A (p.R739H) alteration is located in exon 13 (coding exon 12) of the VEPH1 gene. This alteration results from a G to A substitution at nucleotide position 2216, causing the arginine (R) at amino acid position 739 to be replaced by a histidine (H). 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

0.52

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.67

.;D;D

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

D;.;D

M_CAP

Benign

0.071

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Uncertain

0.047

MutationAssessor

Pathogenic

3.2

.;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.022

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.35

B;B;B

Vest4

0.49

MVP

0.69

MPC

0.080

ClinPred

0.82

GERP RS

4.7

Varity_R

0.25

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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