NM_001167912.2:c.1094G>A

Variant names:

• chr3-157381189-C-T
• rs16827563
• NM_001167912.2:c.1094G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001167912.2(VEPH1):​c.1094G>A​(p.Arg365Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00566 in 1,613,790 control chromosomes in the GnomAD database, including 431 homozygotes. 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: 𝑓 0.030 (230 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (201 hom.)
• Consequence: VEPH1 NM_001167912.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013418794).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEPH1	NM_001167912.2	MANE Select	c.1094G>A	p.Arg365Gln	missense	Exon 7 of 14	NP_001161384.1
	VEPH1	NM_024621.2		c.1094G>A	p.Arg365Gln	missense	Exon 7 of 14	NP_078897.2
	VEPH1	NM_001167911.2		c.1094G>A	p.Arg365Gln	missense	Exon 7 of 13	NP_001161383.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEPH1	ENST00000362010.7	TSL:1 MANE Select	c.1094G>A	p.Arg365Gln	missense	Exon 7 of 14	ENSP00000354919.2
	VEPH1	ENST00000392833.6	TSL:1	c.1094G>A	p.Arg365Gln	missense	Exon 7 of 13	ENSP00000376578.2
	VEPH1	ENST00000392832.6	TSL:2	c.1094G>A	p.Arg365Gln	missense	Exon 7 of 14	ENSP00000376577.2

Frequencies

GnomAD3 genomes AF: 0.0299 AC: 4543 AN: 152052 Hom.: 231 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000832

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0258

GnomAD2 exomes AF: 0.00775 AC: 1949 AN: 251372 AF XY: 0.00556

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.00463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00314 AC: 4585 AN: 1461620 Hom.: 201 Cov.: 30 AF XY: 0.00269 AC XY: 1953 AN XY: 727102

African (AFR) AF: 0.111 AC: 3701 AN: 33476

American (AMR) AF: 0.00588 AC: 263 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00375 AC: 21 AN: 5600

European-Non Finnish (NFE) AF: 0.000147 AC: 164 AN: 1111980

Other (OTH) AF: 0.00696 AC: 420 AN: 60370

GnomAD4 genome AF: 0.0299 AC: 4543 AN: 152170 Hom.: 230 Cov.: 32 AF XY: 0.0285 AC XY: 2121 AN XY: 74396

African (AFR) AF: 0.104 AC: 4308 AN: 41496

American (AMR) AF: 0.0102 AC: 156 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68018

Other (OTH) AF: 0.0256 AC: 54 AN: 2112

Alfa AF: 0.0107 Hom.: 154

Bravo AF: 0.0332

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0987 AC: 435

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0100 AC: 1217

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.67	N
PhyloP100		0.34
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.068
Sift	Benign	0.32	T
Sift4G	Benign	0.71	T
Polyphen		0.028	B
Vest4		0.17
MPC		0.042
ClinPred		0.0036	T
GERP RS		0.81
Varity_R		0.019
gMVP		0.27
Mutation Taster		=100/0	polymorphism (auto)

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: rs16827563; hg19: chr3-157098978; COSMIC: COSV62876724; COSMIC: COSV62876724;