20-37943993-G-A

Position:

• chr20-37943993-G-A

Variant summary

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

The ENST00000373461.9(VSTM2L):​c.355G>A​(p.Val119Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000007 in 1,428,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: VSTM2L ENST00000373461.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.73

Genes affected

VSTM2L (HGNC:16096): (V-set and transmembrane domain containing 2 like) Predicted to enable cell-cell adhesion mediator activity. Involved in negative regulation of neuron apoptotic process. Located in cytoplasm and extracellular region. [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=0.1320323).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSTM2L	NM_080607.3	c.355G>A	p.Val119Met	missense_variant	4/4	ENST00000373461.9	NP_542174.1
VSTM2L	XM_011528530.2	c.304G>A	p.Val102Met	missense_variant	3/3		XP_011526832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSTM2L	ENST00000373461.9	c.355G>A	p.Val119Met	missense_variant	4/4	1	NM_080607.3	ENSP00000362560.4
VSTM2L	ENST00000448944.1	c.304G>A	p.Val102Met	missense_variant	3/3	3		ENSP00000406537.1
VSTM2L	ENST00000373459.4	c.134G>A	p.Gly45Asp	missense_variant	2/2	3		ENSP00000362558.4

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428596 Hom.: 0 Cov.: 45 AF XY: 0.00000142 AC XY: 1 AN XY: 704790

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: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

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

Jan 26, 2022

The c.355G>A (p.V119M) alteration is located in exon 4 (coding exon 4) of the VSTM2L gene. This alteration results from a G to A substitution at nucleotide position 355, causing the valine (V) at amino acid position 119 to be replaced by a methionine (M). 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	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	31
DANN	Uncertain	1.0
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.71	T
MutationTaster	Benign	1.0	D;D;N
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.069
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.26	T
Vest4		0.30
MutPred		0.15		Loss of catalytic residue at L50 (P = 0.1187);
MVP		0.076
ClinPred		0.93	D
GERP RS		4.4

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: chr20-36572395;