20-37903432-G-A

Variant names:

• chr20-37903432-G-A
• rs11550661
• NM_080607.3:c.82G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080607.3(VSTM2L):​c.82G>A​(p.Ala28Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VSTM2L NM_080607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36
• Publications: 0 publications found

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]

ENSG00000305049 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15018371).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080607.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM2L	NM_080607.3	MANE Select	c.82G>A	p.Ala28Thr	missense	Exon 1 of 4	NP_542174.1	Q96N03-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM2L	ENST00000373461.9	TSL:1 MANE Select	c.82G>A	p.Ala28Thr	missense	Exon 1 of 4	ENSP00000362560.4	Q96N03-1
	VSTM2L	ENST00000954389.1		c.82G>A	p.Ala28Thr	missense	Exon 1 of 4	ENSP00000624448.1
	VSTM2L	ENST00000869290.1		c.82G>A	p.Ala28Thr	missense	Exon 1 of 3	ENSP00000539349.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1334904 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 658342

African (AFR) AF: 0.00 AC: 0 AN: 27098

American (AMR) AF: 0.00 AC: 0 AN: 29138

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23622

East Asian (EAS) AF: 0.00 AC: 0 AN: 29032

South Asian (SAS) AF: 0.00 AC: 0 AN: 74528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5548

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1057070

Other (OTH) AF: 0.00 AC: 0 AN: 55612

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.044
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.4
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.056
Sift	Benign	0.042	D
Sift4G	Benign	0.14	T
Polyphen		0.76	P
Vest4		0.34
MutPred		0.27		Gain of loop (P = 0.0013)
MVP		0.15
MPC		0.18
ClinPred		0.46	T
GERP RS		4.6
PromoterAI		0.045	Neutral
Varity_R		0.091
gMVP		0.30
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs11550661; hg19: chr20-36531834;