rs769946306

Variant names:

• chr20-37944042-C-A
• rs769946306
• NM_080607.3:c.404C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-37944042-C-A
• chr20-37944042-C-T

Variant summary

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

The NM_080607.3(VSTM2L):​c.404C>A​(p.Thr135Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VSTM2L NM_080607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.89

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=0.07921848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSTM2L	NM_080607.3	c.404C>A	p.Thr135Lys	missense_variant	Exon 4 of 4	ENST00000373461.9	NP_542174.1
VSTM2L	XM_011528530.2	c.353C>A	p.Thr118Lys	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.404C>A	p.Thr135Lys	missense_variant	Exon 4 of 4	1	NM_080607.3	ENSP00000362560.4
VSTM2L	ENST00000448944.1	c.353C>A	p.Thr118Lys	missense_variant	Exon 3 of 3	3		ENSP00000406537.1
VSTM2L	ENST00000373459.4	c.183C>A	p.His61Gln	missense_variant	Exon 2 of 2	3		ENSP00000362558.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD3 exomes AF: 0.00000406 AC: 1 AN: 246132 Hom.: 0 AF XY: 0.00000749 AC XY: 1 AN XY: 133594

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000330

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1457832 Hom.: 0 Cov.: 45 AF XY: 0.00 AC XY: 0 AN XY: 724482

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Benign	-0.42
CADD	Pathogenic	27
DANN	Uncertain	0.99
Eigen	Benign	-0.080
Eigen_PC	Benign	0.097
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.61	T
Vest4		0.26
MutPred		0.058		Loss of catalytic residue at H61 (P = 0.0572);
MVP		0.040
ClinPred		0.75	D
GERP RS		5.4

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

LitVar

Other links and lift over

dbSNP: rs769946306; hg19: chr20-36572444;