chr19-29529939-C-T

Position:

• chr19-29529939-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001146339.2(VSTM2B):​c.418C>T​(p.His140Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,397,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: VSTM2B NM_001146339.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.835

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16906029).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSTM2B	NM_001146339.2	c.418C>T	p.His140Tyr	missense_variant	4/5	ENST00000335523.8	NP_001139811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSTM2B	ENST00000335523.8	c.418C>T	p.His140Tyr	missense_variant	4/5	5	NM_001146339.2	ENSP00000335038.6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000429 AC: 6 AN: 1397446 Hom.: 0 Cov.: 32 AF XY: 0.00000290 AC XY: 2 AN XY: 689288

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000463

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

The c.418C>T (p.H140Y) alteration is located in exon 4 (coding exon 4) of the VSTM2B gene. This alteration results from a C to T substitution at nucleotide position 418, causing the histidine (H) at amino acid position 140 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.19
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.3	L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.20
Sift	Benign	0.15	T
Sift4G	Benign	0.18	T
Polyphen		0.90	P
Vest4		0.21
MutPred		0.54		Gain of phosphorylation at H140 (P = 0.0152);
MVP		0.19
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.39
gMVP		0.62

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-30020846;