Variant chr11-93820785-A-G 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.517T>C(p.Cys173Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,399,258 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: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

VSTM5
NM_001144871.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03

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:

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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=0.24406421).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSTM5	NM_001144871.2 linkuse as main transcript	c.517T>C	p.Cys173Arg	missense_variant	3/4	ENST00000409977.2	NP_001138343.1	A8MXK1
VSTM5	XR_001747865.2 linkuse as main transcript	n.633T>C		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VSTM5	ENST00000409977.2 linkuse as main transcript	c.517T>C	p.Cys173Arg	missense_variant	3/4	5	NM_001144871.2	ENSP00000386607.1	A8MXK1
VSTM5	ENST00000414919.2 linkuse as main transcript	n.1176T>C		non_coding_transcript_exon_variant	2/2	2
VSTM5	ENST00000398221.3 linkuse as main transcript	n.-27T>C		upstream_gene_variant		3		ENSP00000381277.3	H0Y3Q1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000143

AC:

AN:

1399258

Hom.:

Cov.:

AF XY:

0.0000130

AC XY:

AN XY:

690158

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000167

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

Cov.:

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

Aug 30, 2021

The c.517T>C (p.C173R) alteration is located in exon 3 (coding exon 3) of the VSTM5 gene. This alteration results from a T to C substitution at nucleotide position 517, causing the cysteine (C) at amino acid position 173 to be replaced by an arginine (R). 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

0.56

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.70

M_CAP

Benign

0.0042

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.81

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.10

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0080

Polyphen

0.49

Vest4

0.38

MutPred

0.53

Gain of disorder (P = 0.0102);

MVP

0.25

ClinPred

0.95

GERP RS

5.6

Varity_R

0.70

gMVP

0.53

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over