rs187843947

Variant names:

• chr10-49047041-G-A
• rs187843947
• NM_001031746.5:c.779C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-49047041-G-A
• chr10-49047041-G-C
• chr10-49047041-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001031746.5(VSTM4):​c.779C>T​(p.Pro260Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: VSTM4 NM_001031746.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.44
• Publications: 2 publications found

Genes affected

VSTM4 (HGNC:26470): (V-set and transmembrane domain containing 4) Predicted to act upstream of or within several processes, including endothelial cell migration; retina blood vessel maintenance; and vasculature development. Predicted to be located in extracellular region and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031746.5. 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
	VSTM4	NM_001031746.5	MANE Select	c.779C>T	p.Pro260Leu	missense	Exon 7 of 8	NP_001026916.2	Q8IW00-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM4	ENST00000332853.9	TSL:1 MANE Select	c.779C>T	p.Pro260Leu	missense	Exon 7 of 8	ENSP00000331062.3	Q8IW00-1
	VSTM4	ENST00000956395.1		c.992C>T	p.Pro331Leu	missense	Exon 8 of 9	ENSP00000626454.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152132 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000477 AC: 12 AN: 251466 AF XY: 0.0000515

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000246 AC: 36 AN: 1461868 Hom.: 0 Cov.: 30 AF XY: 0.0000261 AC XY: 19 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

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

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

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152250 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74444

African (AFR) AF: 0.00 AC: 0 AN: 41530

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

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: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000494 AC: 6

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	0.27
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0098	T
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		5.4
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.18
Sift	Uncertain	0.020	D
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.81
MVP		0.31
MPC		0.51
ClinPred		0.85	D
GERP RS		5.9
Varity_R		0.20
gMVP		0.36
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs187843947; hg19: chr10-50255086; COSMIC: COSV60525348;