3-157363464-A-T

Position:

• chr3-157363464-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001167912.2(VEPH1):​c.1635T>A​(p.Asp545Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 2.50

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VEPH1	NM_001167912.2	c.1635T>A	p.Asp545Glu	missense_variant	9/14	ENST00000362010.7	NP_001161384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEPH1	ENST00000362010.7	c.1635T>A	p.Asp545Glu	missense_variant	9/14	1	NM_001167912.2	ENSP00000354919.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jul 26, 2024

The c.1635T>A (p.D545E) alteration is located in exon 9 (coding exon 8) of the VEPH1 gene. This alteration results from a T to A substitution at nucleotide position 1635, causing the aspartic acid (D) at amino acid position 545 to be replaced by a glutamic acid (E). 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	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.62	.;D;D
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.85	D;.;D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.4	M;M;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.80
MutPred		0.46		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		0.39
MPC		0.28
ClinPred		0.99	D
GERP RS		3.1
Varity_R		0.63
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-157081253;