rs377435668

Variant names:

• chr20-37944173-G-A
• rs377435668
• NM_080607.3:c.535G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-37944173-G-A
• chr20-37944173-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080607.3(VSTM2L):​c.535G>A​(p.Ala179Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000464 in 1,423,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A179P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000021 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: VSTM2L NM_080607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.192
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048061788).

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.535G>A	p.Ala179Thr	missense	Exon 4 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.535G>A	p.Ala179Thr	missense	Exon 4 of 4	ENSP00000362560.4	Q96N03-1
	VSTM2L	ENST00000954389.1		c.523G>A	p.Ala175Thr	missense	Exon 4 of 4	ENSP00000624448.1
	VSTM2L	ENST00000869290.1		c.472G>A	p.Ala158Thr	missense	Exon 3 of 3	ENSP00000539349.1

Frequencies

GnomAD3 genomes AF: 0.0000205 AC: 3 AN: 146224 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000503

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000128 AC: 2 AN: 156240 AF XY: 0.0000118

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000335

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000493 AC: 63 AN: 1277212 Hom.: 0 Cov.: 45 AF XY: 0.0000445 AC XY: 28 AN XY: 628590

African (AFR) AF: 0.0000703 AC: 2 AN: 28458

American (AMR) AF: 0.00 AC: 0 AN: 33336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20750

East Asian (EAS) AF: 0.00 AC: 0 AN: 28080

South Asian (SAS) AF: 0.00 AC: 0 AN: 78650

European-Finnish (FIN) AF: 0.0000273 AC: 1 AN: 36570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4168

European-Non Finnish (NFE) AF: 0.0000592 AC: 59 AN: 997114

Other (OTH) AF: 0.0000200 AC: 1 AN: 50086

GnomAD4 genome AF: 0.0000205 AC: 3 AN: 146224 Hom.: 0 Cov.: 28 AF XY: 0.0000421 AC XY: 3 AN XY: 71204

African (AFR) AF: 0.0000503 AC: 2 AN: 39776

American (AMR) AF: 0.00 AC: 0 AN: 14772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3420

East Asian (EAS) AF: 0.00 AC: 0 AN: 4726

South Asian (SAS) AF: 0.00 AC: 0 AN: 4428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000151 AC: 1 AN: 66400

Other (OTH) AF: 0.00 AC: 0 AN: 2002

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000362 AC: 3

ExAC AF: 0.0000188 AC: 2

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	0.078
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.19
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.071
Sift	Benign	0.40	T
Sift4G	Benign	0.24	T
Polyphen		0.0090	B
Vest4		0.12
MVP		0.092
MPC		0.25
ClinPred		0.071	T
GERP RS		2.9
Varity_R		0.066
gMVP		0.19
Mutation Taster		=95/5	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: rs377435668; hg19: chr20-36572575; COSMIC: COSV65095745; COSMIC: COSV65095745;