chr20-37944114-C-T

Variant names:

• chr20-37944114-C-T
• NM_080607.3:c.476C>T

Variant summary

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

The NM_080607.3(VSTM2L):​c.476C>T​(p.Ala159Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: VSTM2L NM_080607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSTM2L	NM_080607.3	c.476C>T	p.Ala159Val	missense_variant	Exon 4 of 4	ENST00000373461.9	NP_542174.1
VSTM2L	XM_011528530.2	c.425C>T	p.Ala142Val	missense_variant	Exon 3 of 3		XP_011526832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSTM2L	ENST00000373461.9	c.476C>T	p.Ala159Val	missense_variant	Exon 4 of 4	1	NM_080607.3	ENSP00000362560.4
VSTM2L	ENST00000448944.1	c.425C>T	p.Ala142Val	missense_variant	Exon 3 of 3	3		ENSP00000406537.1
VSTM2L	ENST00000373459.4	c.255C>T	p.Gly85Gly	synonymous_variant	Exon 2 of 2	3		ENSP00000362558.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.476C>T (p.A159V) alteration is located in exon 4 (coding exon 4) of the VSTM2L gene. This alteration results from a C to T substitution at nucleotide position 476, causing the alanine (A) at amino acid position 159 to be replaced by a valine (V). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	T;.
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.9	D;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	D;.
Vest4		0.78
MutPred		0.64		Loss of sheet (P = 0.0025);.;
MVP		0.18
MPC		0.73
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.69
gMVP		0.56

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: chr20-36572516;