chr19-29526624-C-T

Variant names:

• chr19-29526624-C-T
• NM_001146339.2:c.41C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001146339.2(VSTM2B):​c.41C>T​(p.Pro14Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000725 in 1,378,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: VSTM2B NM_001146339.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.105181456).

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.41C>T	p.Pro14Leu	missense	Exon 1 of 5	NP_001139811.1	A6NLU5
	VSTM2B	NM_001384640.1		c.41C>T	p.Pro14Leu	missense	Exon 1 of 4	NP_001371569.1
	VSTM2B	NM_001384641.1		c.-56-587C>T		intron	N/A	NP_001371570.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM2B	ENST00000335523.8	TSL:5 MANE Select	c.41C>T	p.Pro14Leu	missense	Exon 1 of 5	ENSP00000335038.6	A6NLU5
	VSTM2B	ENST00000915703.1		c.41C>T	p.Pro14Leu	missense	Exon 2 of 7	ENSP00000585762.1
	VSTM2B	ENST00000952478.1		c.41C>T	p.Pro14Leu	missense	Exon 1 of 6	ENSP00000622537.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.25e-7 AC: 1 AN: 1378710 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 680354

African (AFR) AF: 0.00 AC: 0 AN: 30868

American (AMR) AF: 0.00 AC: 0 AN: 35228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24984

East Asian (EAS) AF: 0.00 AC: 0 AN: 35188

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 78206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5524

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076046

Other (OTH) AF: 0.00 AC: 0 AN: 57642

GnomAD4 genome Cov.: 31

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	0.099
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.00086	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.34	N
PhyloP100		1.0
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.21	N
REVEL	Benign	0.11
Sift	Benign	0.66	T
Sift4G	Benign	0.98	T
Polyphen		0.0010	B
Vest4		0.29
MutPred		0.39		Loss of loop (P = 0.0153)
MVP		0.076
ClinPred		0.49	T
GERP RS		0.77
Varity_R		0.037
gMVP		0.54
Mutation Taster		=86/14	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

hg19: chr19-30017531;