11-93820807-G-T

Position:

• chr11-93820807-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001144871.2(VSTM5):​c.495C>A​(p.Ser165Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: VSTM5 NM_001144871.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSTM5	NM_001144871.2	c.495C>A	p.Ser165Arg	missense_variant	3/4	ENST00000409977.2	NP_001138343.1
VSTM5	XR_001747865.2	n.611C>A		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSTM5	ENST00000409977.2	c.495C>A	p.Ser165Arg	missense_variant	3/4	5	NM_001144871.2	ENSP00000386607	P1
VSTM5	ENST00000414919.2	n.1154C>A		non_coding_transcript_exon_variant	2/2	2
VSTM5	ENST00000398221.3			upstream_gene_variant		3		ENSP00000381277

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2023

The c.495C>A (p.S165R) alteration is located in exon 3 (coding exon 3) of the VSTM5 gene. This alteration results from a C to A substitution at nucleotide position 495, causing the serine (S) at amino acid position 165 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	Pathogenic	0.98
BayesDel_addAF	Benign	0.0062	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0079	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.81	L
MutationTaster	Benign	0.73	N
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.24
Sift	Benign	0.10	T
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.65
MutPred		0.55		Gain of MoRF binding (P = 0.012);
MVP		0.095
ClinPred		0.84	D
GERP RS		3.6
Varity_R		0.20
gMVP		0.75

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.

Other links and lift over

hg19: chr11-93553973;