3-157363721-C-T

Variant names:

• chr3-157363721-C-T
• rs201025388
• NM_001167912.2:c.1378G>A

Variant summary

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

The NM_001167912.2(VEPH1):​c.1378G>A​(p.Val460Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,614,126 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (1 hom.)
• Consequence: VEPH1 NM_001167912.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.05
• Publications: 4 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=0.017021447).

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.1378G>A	p.Val460Met	missense	Exon 9 of 14	NP_001161384.1	Q14D04-1
	VEPH1	NM_024621.2		c.1378G>A	p.Val460Met	missense	Exon 9 of 14	NP_078897.2	Q14D04-1
	VEPH1	NM_001167911.2		c.1378G>A	p.Val460Met	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.1378G>A	p.Val460Met	missense	Exon 9 of 14	ENSP00000354919.2	Q14D04-1
	VEPH1	ENST00000392833.6	TSL:1	c.1378G>A	p.Val460Met	missense	Exon 9 of 13	ENSP00000376578.2	Q14D04-2
	VEPH1	ENST00000392832.6	TSL:2	c.1378G>A	p.Val460Met	missense	Exon 9 of 14	ENSP00000376577.2	Q14D04-1

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000199 AC: 50 AN: 250810 AF XY: 0.000162

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.000521

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000247

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000223 AC: 326 AN: 1461838 Hom.: 1 Cov.: 33 AF XY: 0.000213 AC XY: 155 AN XY: 727222

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000514 AC: 23 AN: 44722

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000258 AC: 287 AN: 1111980

Other (OTH) AF: 0.000232 AC: 14 AN: 60394

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152288 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74468

African (AFR) AF: 0.000144 AC: 6 AN: 41566

American (AMR) AF: 0.000523 AC: 8 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68014

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000261 Hom.: 2

Bravo AF: 0.000280

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000148 AC: 18

EpiCase AF: 0.000218

EpiControl AF: 0.000237

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	0.071
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.79
DANN	Benign	0.95
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L
PhyloP100		-2.1
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.020
Sift	Benign	0.14	T
Sift4G	Benign	0.14	T
Polyphen		0.0050	B
Vest4		0.10
MVP		0.095
MPC		0.039
ClinPred		0.015	T
GERP RS		-0.90
Varity_R		0.031
gMVP		0.18
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs201025388; hg19: chr3-157081510; COSMIC: COSV62880700;