Variant 3-157363478-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001167912.2(VEPH1):c.1621A>G(p.Ile541Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

VEPH1
NM_001167912.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.503

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017572224).

BP6

Variant 3-157363478-T-C is Benign according to our data. Variant chr3-157363478-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2257237.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VEPH1	NM_001167912.2 linkuse as main transcript	c.1621A>G	p.Ile541Val	missense_variant	9/14	ENST00000362010.7	NP_001161384.1
LOC101928236	XR_007096141.1 linkuse as main transcript	n.7553-7925T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEPH1	ENST00000362010.7 linkuse as main transcript	c.1621A>G	p.Ile541Val	missense_variant	9/14	1	NM_001167912.2	ENSP00000354919	P1	Q14D04-1
	ENST00000487238.5 linkuse as main transcript	n.332-17636T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251066

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.051

DANN

Benign

0.65

DEOGEN2

Benign

0.014

.;T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.36

T;.;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.018

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.29

N;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

0.24

N;N;N

REVEL

Benign

0.032

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.57

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.053

MutPred

0.16

Gain of glycosylation at Y543 (P = 0.0162);Gain of glycosylation at Y543 (P = 0.0162);Gain of glycosylation at Y543 (P = 0.0162);

MVP

0.11

MPC

0.034

ClinPred

0.018

GERP RS

-4.5

Varity_R

0.028

gMVP

0.092

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