chr20-37903370-T-C

Position:

• chr20-37903370-T-C

Variant summary

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

The NM_080607.3(VSTM2L):​c.20T>C​(p.Val7Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,327,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000015 (0 hom.)
• Consequence: VSTM2L NM_080607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.309

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]

LOC124904896 (HGNC:):

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=0.15498969).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSTM2L	NM_080607.3	c.20T>C	p.Val7Ala	missense_variant	1/4	ENST00000373461.9	NP_542174.1
VSTM2L	XM_011528530.2	c.20T>C	p.Val7Ala	missense_variant	1/3		XP_011526832.1
LOC124904896	XR_007067576.1	n.3611+3249A>G		intron_variant
LOC124904896	XR_007067577.1	n.543+3249A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSTM2L	ENST00000373461.9	c.20T>C	p.Val7Ala	missense_variant	1/4	1	NM_080607.3	ENSP00000362560.4
VSTM2L	ENST00000448944.1	c.20T>C	p.Val7Ala	missense_variant	1/3	3		ENSP00000406537.1
VSTM2L	ENST00000373459.4	c.20T>C	p.Val7Ala	missense_variant	1/2	3		ENSP00000362558.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000151 AC: 2 AN: 1327496 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 654622

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000704

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000756

Asia WGS AF: 0.000292 AC: 1 AN: 3438

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

Feb 27, 2023

The c.20T>C (p.V7A) alteration is located in exon 1 (coding exon 1) of the VSTM2L gene. This alteration results from a T to C substitution at nucleotide position 20, causing the valine (V) at amino acid position 7 to be replaced by an alanine (A). 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	0.063
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0045	T;.;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.44	T;T;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.070	N;N;N
REVEL	Benign	0.075
Sift	Uncertain	0.010	D;D;D
Sift4G	Benign	0.53	T;T;T
Polyphen		0.81	P;.;.
Vest4		0.18
MutPred		0.37		Gain of helix (P = 6e-04);Gain of helix (P = 6e-04);Gain of helix (P = 6e-04);
MVP		0.25
MPC		0.25
ClinPred		0.18	T
GERP RS		-1.7
Varity_R		0.040
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs1051092323; hg19: chr20-36531772;