20-37944027-C-T

Position:

• chr20-37944027-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000373461.9(VSTM2L):​c.389C>T​(p.Ser130Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 28)
• Consequence: VSTM2L ENST00000373461.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.09

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.857

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSTM2L	NM_080607.3	c.389C>T	p.Ser130Phe	missense_variant	4/4	ENST00000373461.9	NP_542174.1
VSTM2L	XM_011528530.2	c.338C>T	p.Ser113Phe	missense_variant	3/3		XP_011526832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSTM2L	ENST00000373461.9	c.389C>T	p.Ser130Phe	missense_variant	4/4	1	NM_080607.3	ENSP00000362560.4
VSTM2L	ENST00000448944.1	c.338C>T	p.Ser113Phe	missense_variant	3/3	3		ENSP00000406537.1
VSTM2L	ENST00000373459.4	c.168C>T	p.Val56Val	synonymous_variant	2/2	3		ENSP00000362558.4

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 45

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 06, 2023

The c.389C>T (p.S130F) 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 389, causing the serine (S) at amino acid position 130 to be replaced by a phenylalanine (F). 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	0.99
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;.
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Uncertain	0.077	D
MutationAssessor	Pathogenic	3.0	M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-6.0	D;D
REVEL	Pathogenic	0.78
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.87
MutPred		0.53		Loss of disorder (P = 0.0118);.;
MVP		0.57
MPC		0.78
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.90
gMVP		0.65

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: chr20-36572429;