Genetic Variant NM_001144871.2:c.290T>C (chr11-93821125-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001144871.2(VSTM5):c.290T>C(p.Val97Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00002 in 1,551,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

VSTM5
NM_001144871.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.63

Variant links:

Genes affected

VSTM5 (HGNC:34443): (V-set and transmembrane domain containing 5) Predicted to be involved in filopodium assembly; positive regulation of excitatory synapse assembly; and protein homooligomerization. Predicted to act upstream of or within ventral spinal cord development. Predicted to be located in axon; dendrite; and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

VSTM5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.18333298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSTM5	NM_001144871.2 link	c.290T>C	p.Val97Ala	missense_variant	Exon 2 of 4	ENST00000409977.2	NP_001138343.1	A8MXK1
VSTM5	XR_001747865.2 link	n.406T>C		non_coding_transcript_exon_variant	Exon 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSTM5	ENST00000409977.2 link	c.290T>C	p.Val97Ala	missense_variant	Exon 2 of 4	5	NM_001144871.2	ENSP00000386607.1		A8MXK1
VSTM5	ENST00000414919.2 link	n.949T>C		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0000857

AC:

AN:

151702

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000315

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000190

AC:

AN:

158070

Hom.:

AF XY:

0.0000120

AC XY:

AN XY:

83444

show subpopulations

Gnomad AFR exome

AF:

0.000245

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000129

AC:

AN:

1399796

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

690398

show subpopulations

Gnomad4 AFR exome

AF:

0.000475

Gnomad4 AMR exome

AF:

0.0000280

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:

0.0000344

GnomAD4 genome

AF:

0.0000857

AC:

AN:

151702

Hom.:

Cov.:

AF XY:

0.0000810

AC XY:

AN XY:

74074

show subpopulations

Gnomad4 AFR

AF:

0.000315

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.000208

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 14, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.290T>C (p.V97A) alteration is located in exon 2 (coding exon 2) of the VSTM5 gene. This alteration results from a T to C substitution at nucleotide position 290, causing the valine (V) at amino acid position 97 to be replaced by an alanine (A). 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

Uncertain

0.51

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.074

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.68

M_CAP

Benign

0.012

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.13

Sift

Benign

0.12

Sift4G

Uncertain

0.018

Polyphen

0.31

Vest4

0.27

MVP

0.014

ClinPred

0.17

GERP RS

5.7

Varity_R

0.22

gMVP

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over