rs753516492

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080607.3(VSTM2L):​c.316G>A​(p.Ala106Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A106S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

VSTM2L
NM_080607.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0220

Publications

0 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.017776579).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VSTM2LNM_080607.3 linkc.316G>A p.Ala106Thr missense_variant Exon 3 of 4 ENST00000373461.9 NP_542174.1 Q96N03-1
VSTM2LXM_011528530.2 linkc.291+1759G>A intron_variant Intron 2 of 2 XP_011526832.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VSTM2LENST00000373461.9 linkc.316G>A p.Ala106Thr missense_variant Exon 3 of 4 1 NM_080607.3 ENSP00000362560.4 Q96N03-1
VSTM2LENST00000448944.1 linkc.291+1759G>A intron_variant Intron 2 of 2 3 ENSP00000406537.1 Q96N03-2
VSTM2LENST00000373459.4 linkc.122-10418G>A intron_variant Intron 1 of 1 3 ENSP00000362558.4 Q96N03-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251240
AF XY:
0.00
show subpopulations
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000343
AC:
5
AN:
1459004
Hom.:
0
Cov.:
34
AF XY:
0.00000276
AC XY:
2
AN XY:
725850
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33366
American (AMR)
AF:
0.00
AC:
0
AN:
44642
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25984
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39408
South Asian (SAS)
AF:
0.0000232
AC:
2
AN:
86222
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53220
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5744
European-Non Finnish (NFE)
AF:
0.00000270
AC:
3
AN:
1110254
Other (OTH)
AF:
0.00
AC:
0
AN:
60164
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.058
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
9.0
DANN
Benign
0.61
DEOGEN2
Benign
0.0050
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.51
T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.018
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-0.29
N
PhyloP100
0.022
PrimateAI
Benign
0.36
T
PROVEAN
Benign
1.0
N
REVEL
Benign
0.021
Sift
Benign
0.59
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.071
MutPred
0.28
Gain of relative solvent accessibility (P = 0.0166);
MVP
0.014
MPC
0.18
ClinPred
0.031
T
GERP RS
-2.5
Varity_R
0.033
gMVP
0.22
Mutation Taster
=74/26
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs753516492; hg19: chr20-36561965; API