Variant 11-93821047-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001144871.2(VSTM5):c.368C>T(p.Thr123Met) variant causes a missense change. The variant allele was found at a frequency of 0.000104 in 1,551,716 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 0.00045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

VSTM5
NM_001144871.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.97

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:

VSTM5 (HGNC:):

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=0.068668514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSTM5	NM_001144871.2 linkuse as main transcript	c.368C>T	p.Thr123Met	missense_variant	2/4	ENST00000409977.2	NP_001138343.1	A8MXK1
VSTM5	XR_001747865.2 linkuse as main transcript	n.484C>T		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSTM5	ENST00000409977.2 linkuse as main transcript	c.368C>T	p.Thr123Met	missense_variant	2/4	5	NM_001144871.2	ENSP00000386607.1		A8MXK1
VSTM5	ENST00000414919.2 linkuse as main transcript	n.1027C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000453

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000115

AC:

AN:

156230

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

82792

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000176

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000663

Gnomad OTH exome

AF:

0.000228

GnomAD4 exome

AF:

0.0000657

AC:

AN:

1399414

Hom.:

Cov.:

AF XY:

0.0000695

AC XY:

AN XY:

690208

show subpopulations

Gnomad4 AFR exome

AF:

0.000949

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000454

Gnomad4 OTH exome

AF:

0.0000517

GnomAD4 genome

AF:

0.000453

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.0000654

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:

0.000261

Hom.:

Bravo

AF:

0.000393

ESP6500AA

AF:

0.00145

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000116

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.368C>T (p.T123M) alteration is located in exon 2 (coding exon 2) of the VSTM5 gene. This alteration results from a C to T substitution at nucleotide position 368, causing the threonine (T) at amino acid position 123 to be replaced by a methionine (M). 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

Benign

0.13

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.082

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.069

MetaSVM

Benign

-0.30

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

0.89

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.23

Sift

Benign

0.044

Sift4G

Benign

0.072

Polyphen

1.0

Vest4

0.20

MVP

0.34

ClinPred

0.10

GERP RS

4.5

Varity_R

0.12

gMVP

0.55

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