3-157363703-C-G

Variant names:

• chr3-157363703-C-G
• rs143505735
• NM_001167912.2:c.1396G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001167912.2(VEPH1):​c.1396G>C​(p.Glu466Gln) 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. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. E466K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VEPH1 NM_001167912.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13
• Publications: 2 publications found

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]

LINC00881 (HGNC:48567): (long intergenic non-protein coding RNA 881)

LOC101928236 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053938717).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001167912.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEPH1	NM_001167912.2	MANE Select	c.1396G>C	p.Glu466Gln	missense	Exon 9 of 14	NP_001161384.1	Q14D04-1
	VEPH1	NM_024621.2		c.1396G>C	p.Glu466Gln	missense	Exon 9 of 14	NP_078897.2	Q14D04-1
	VEPH1	NM_001167911.2		c.1396G>C	p.Glu466Gln	missense	Exon 9 of 13	NP_001161383.1	Q14D04-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEPH1	ENST00000362010.7	TSL:1 MANE Select	c.1396G>C	p.Glu466Gln	missense	Exon 9 of 14	ENSP00000354919.2	Q14D04-1
	VEPH1	ENST00000392833.6	TSL:1	c.1396G>C	p.Glu466Gln	missense	Exon 9 of 13	ENSP00000376578.2	Q14D04-2
	VEPH1	ENST00000392832.6	TSL:2	c.1396G>C	p.Glu466Gln	missense	Exon 9 of 14	ENSP00000376577.2	Q14D04-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 250942 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.8
DANN	Benign	0.41
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.81	L
PhyloP100		2.1
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.024
Sift	Benign	0.55	T
Sift4G	Benign	0.50	T
Polyphen		0.0050	B
Vest4		0.077
MutPred		0.12		Gain of glycosylation at S462 (P = 0.0423)
MVP		0.20
MPC		0.039
ClinPred		0.064	T
GERP RS		4.5
Varity_R		0.17
gMVP		0.28
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs143505735; hg19: chr3-157081492;