3-157381189-C-T

Variant names:

• chr3-157381189-C-T
• rs16827563
• NM_001167912.2:c.1094G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001167912.2(VEPH1):​c.1094G>A​(p.Arg365Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00566 in 1,613,790 control chromosomes in the GnomAD database, including 431 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.030 (230 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (201 hom.)
• Consequence: VEPH1 NM_001167912.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337

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]

ENSG00000243176 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013418794).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEPH1	NM_001167912.2	c.1094G>A	p.Arg365Gln	missense_variant	Exon 7 of 14	ENST00000362010.7	NP_001161384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VEPH1	ENST00000362010.7	c.1094G>A	p.Arg365Gln	missense_variant	Exon 7 of 14	1	NM_001167912.2	ENSP00000354919.2

Frequencies

GnomAD3 genomes AF: 0.0299 AC: 4543 AN: 152052 Hom.: 231 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000832

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0258

GnomAD3 exomes AF: 0.00775 AC: 1949 AN: 251372 Hom.: 99 AF XY: 0.00556 AC XY: 755 AN XY: 135840

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.00463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00314 AC: 4585 AN: 1461620 Hom.: 201 Cov.: 30 AF XY: 0.00269 AC XY: 1953 AN XY: 727102

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.00588

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000147

Gnomad4 OTH exome AF: 0.00696

GnomAD4 genome AF: 0.0299 AC: 4543 AN: 152170 Hom.: 230 Cov.: 32 AF XY: 0.0285 AC XY: 2121 AN XY: 74396

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.00546 Hom.: 56

Bravo AF: 0.0332

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0987 AC: 435

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0100 AC: 1217

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.040	.;T;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.84	T;.;T
MetaRNN	Benign	0.0013	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.67	N;N;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.35	N;N;N
REVEL	Benign	0.068
Sift	Benign	0.32	T;T;T
Sift4G	Benign	0.71	T;T;T
Polyphen		0.028	B;B;B
Vest4		0.17
MPC		0.042
ClinPred		0.0036	T
GERP RS		0.81
Varity_R		0.019
gMVP		0.27

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

Other links and lift over

dbSNP: rs16827563; hg19: chr3-157098978; COSMIC: COSV62876724; COSMIC: COSV62876724;