3-157317132-C-T

Variant names:

• chr3-157317132-C-T
• rs145883418
• NM_001167912.2:c.1805G>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.1805G>A​(p.Ser602Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000885 in 1,613,696 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00083 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00089 (1 hom.)
• Consequence: VEPH1 NM_001167912.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.56
• Publications: 6 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=0.02150172).

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.1805G>A	p.Ser602Asn	missense	Exon 10 of 14	NP_001161384.1	Q14D04-1
	VEPH1	NM_024621.2		c.1805G>A	p.Ser602Asn	missense	Exon 10 of 14	NP_078897.2	Q14D04-1
	VEPH1	NM_001167911.2		c.1805G>A	p.Ser602Asn	missense	Exon 10 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.1805G>A	p.Ser602Asn	missense	Exon 10 of 14	ENSP00000354919.2	Q14D04-1
	VEPH1	ENST00000392833.6	TSL:1	c.1805G>A	p.Ser602Asn	missense	Exon 10 of 13	ENSP00000376578.2	Q14D04-2
	VEPH1	ENST00000392832.6	TSL:2	c.1805G>A	p.Ser602Asn	missense	Exon 10 of 14	ENSP00000376577.2	Q14D04-1

Frequencies

GnomAD3 genomes AF: 0.000834 AC: 127 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000911

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.000713 AC: 179 AN: 251122 AF XY: 0.000774

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000870

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000960

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000890 AC: 1301 AN: 1461382 Hom.: 1 Cov.: 30 AF XY: 0.000916 AC XY: 666 AN XY: 726998

African (AFR) AF: 0.000239 AC: 8 AN: 33460

American (AMR) AF: 0.000604 AC: 27 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.000191 AC: 5 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.000882 AC: 76 AN: 86194

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53416

Middle Eastern (MID) AF: 0.00607 AC: 35 AN: 5762

European-Non Finnish (NFE) AF: 0.000985 AC: 1095 AN: 1111764

Other (OTH) AF: 0.000895 AC: 54 AN: 60368

GnomAD4 genome AF: 0.000834 AC: 127 AN: 152314 Hom.: 0 Cov.: 32 AF XY: 0.000926 AC XY: 69 AN XY: 74480

African (AFR) AF: 0.000241 AC: 10 AN: 41572

American (AMR) AF: 0.00301 AC: 46 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000911 AC: 62 AN: 68024

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.000767 Hom.: 0

Bravo AF: 0.000793

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000766 AC: 93

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00175

EpiControl AF: 0.00160

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	0.34
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.55
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.092	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.6
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.10
Sift	Benign	0.15	T
Sift4G	Uncertain	0.013	D
Polyphen		0.66	P
Vest4		0.48
MVP		0.43
MPC		0.25
ClinPred		0.043	T
GERP RS		5.6
Varity_R		0.24
gMVP		0.36
Mutation Taster		=82/18	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: rs145883418; hg19: chr3-157034921;