3-157381192-G-T

Position:

• chr3-157381192-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001167912.2(VEPH1):​c.1091C>A​(p.Thr364Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: 32)
• Consequence: VEPH1 NM_001167912.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059083432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VEPH1	NM_001167912.2	c.1091C>A	p.Thr364Asn	missense_variant	7/14	ENST00000362010.7	NP_001161384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEPH1	ENST00000362010.7	c.1091C>A	p.Thr364Asn	missense_variant	7/14	1	NM_001167912.2	ENSP00000354919.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2024

The c.1091C>A (p.T364N) alteration is located in exon 7 (coding exon 6) of the VEPH1 gene. This alteration results from a C to A substitution at nucleotide position 1091, causing the threonine (T) at amino acid position 364 to be replaced by an asparagine (N). 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	Benign	0.094
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.027	.;T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.63	T;.;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.059	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.6	L;L;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.51	N;N;N
REVEL	Benign	0.071
Sift	Benign	0.26	T;T;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.0060	B;B;B
Vest4		0.34
MutPred		0.15		Gain of glycosylation at T364 (P = 0.0842);Gain of glycosylation at T364 (P = 0.0842);Gain of glycosylation at T364 (P = 0.0842);
MVP		0.081
MPC		0.042
ClinPred		0.14	T
GERP RS		4.5
Varity_R		0.047
gMVP		0.34

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: rs1160968430; hg19: chr3-157098981;