rs751468685

Variant names:

• chr19-29527270-C-T
• rs751468685
• NM_001146339.2:c.142C>T

Variant summary

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

The NM_001146339.2(VSTM2B):​c.142C>T​(p.Pro48Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000645 in 1,550,368 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: VSTM2B NM_001146339.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57
• Publications: 0 publications found

Genes affected

VSTM2B (HGNC:33595): (V-set and transmembrane domain containing 2B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

VSTM2B-DT (HGNC:27615): (VSTM2B divergent transcript)

LOC124904683 (HGNC:):

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_001146339.2. 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
	VSTM2B	NM_001146339.2	MANE Select	c.142C>T	p.Pro48Ser	missense	Exon 2 of 5	NP_001139811.1	A6NLU5
	VSTM2B	NM_001384640.1		c.142C>T	p.Pro48Ser	missense	Exon 2 of 4	NP_001371569.1
	VSTM2B	NM_001384641.1		c.4C>T	p.Pro2Ser	missense	Exon 2 of 5	NP_001371570.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM2B	ENST00000335523.8	TSL:5 MANE Select	c.142C>T	p.Pro48Ser	missense	Exon 2 of 5	ENSP00000335038.6	A6NLU5
	VSTM2B	ENST00000915703.1		c.142C>T	p.Pro48Ser	missense	Exon 3 of 7	ENSP00000585762.1
	VSTM2B	ENST00000952478.1		c.142C>T	p.Pro48Ser	missense	Exon 2 of 6	ENSP00000622537.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000321 AC: 5 AN: 155786 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000163

Gnomad ASJ exome AF: 0.000118

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000501 AC: 7 AN: 1398160 Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1 AN XY: 689588

African (AFR) AF: 0.0000317 AC: 1 AN: 31570

American (AMR) AF: 0.0000841 AC: 3 AN: 35684

Ashkenazi Jewish (ASJ) AF: 0.0000795 AC: 2 AN: 25162

East Asian (EAS) AF: 0.00 AC: 0 AN: 35696

South Asian (SAS) AF: 0.00 AC: 0 AN: 79134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078786

Other (OTH) AF: 0.00 AC: 0 AN: 57970

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152208 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000382 AC: 1

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	Pathogenic	0.58
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.6
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.26
Sift	Benign	0.48	T
Sift4G	Benign	0.43	T
Polyphen		0.99	D
Vest4		0.52
MutPred		0.65		Loss of catalytic residue at P48 (P = 0.0109)
MVP		0.28
ClinPred		0.45	T
GERP RS		4.5
Varity_R		0.16
gMVP		0.67
Mutation Taster		=27/73	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs751468685; hg19: chr19-30018177; COSMIC: COSV59263375; COSMIC: COSV59263375;