rs143505735

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-157363703-C-T
• chr3-157363703-C-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001167912.2(VEPH1):​c.1396G>A​(p.Glu466Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,614,056 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00063 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (1 hom.)
• Consequence: VEPH1 NM_001167912.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009025186).

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>A	p.Glu466Lys	missense	Exon 9 of 14	NP_001161384.1	Q14D04-1
	VEPH1	NM_024621.2		c.1396G>A	p.Glu466Lys	missense	Exon 9 of 14	NP_078897.2	Q14D04-1
	VEPH1	NM_001167911.2		c.1396G>A	p.Glu466Lys	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>A	p.Glu466Lys	missense	Exon 9 of 14	ENSP00000354919.2	Q14D04-1
	VEPH1	ENST00000392833.6	TSL:1	c.1396G>A	p.Glu466Lys	missense	Exon 9 of 13	ENSP00000376578.2	Q14D04-2
	VEPH1	ENST00000392832.6	TSL:2	c.1396G>A	p.Glu466Lys	missense	Exon 9 of 14	ENSP00000376577.2	Q14D04-1

Frequencies

GnomAD3 genomes AF: 0.000612 AC: 93 AN: 152084 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00200

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000235 AC: 59 AN: 250942 AF XY: 0.000206

Gnomad AFR exome AF: 0.00229

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000110 AC: 161 AN: 1461854 Hom.: 1 Cov.: 33 AF XY: 0.000105 AC XY: 76 AN XY: 727224

African (AFR) AF: 0.00176 AC: 59 AN: 33480

American (AMR) AF: 0.000134 AC: 6 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.000394 AC: 34 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000450 AC: 50 AN: 1111992

Other (OTH) AF: 0.000182 AC: 11 AN: 60392

GnomAD4 genome AF: 0.000631 AC: 96 AN: 152202 Hom.: 1 Cov.: 32 AF XY: 0.000685 AC XY: 51 AN XY: 74412

African (AFR) AF: 0.00207 AC: 86 AN: 41522

American (AMR) AF: 0.000262 AC: 4 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68014

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.000483 Hom.: 1

Bravo AF: 0.000672

ESP6500AA AF: 0.00363 AC: 16

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000231 AC: 28

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.0090	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.1
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.032
Sift	Benign	0.11	T
Sift4G	Benign	0.20	T
Polyphen		0.52	P
Vest4		0.22
MVP		0.16
MPC		0.042
ClinPred		0.022	T
GERP RS		4.5
Varity_R		0.16
gMVP		0.30
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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;