chr11-93821035-C-T

Variant names:

• chr11-93821035-C-T
• NM_001144871.2:c.380G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001144871.2(VSTM5):​c.380G>A​(p.Gly127Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: VSTM5 NM_001144871.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.15

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSTM5	NM_001144871.2	c.380G>A	p.Gly127Glu	missense_variant	Exon 2 of 4	ENST00000409977.2	NP_001138343.1
VSTM5	XR_001747865.2	n.496G>A		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	c.380G>A	p.Gly127Glu	missense_variant	Exon 2 of 4	5	NM_001144871.2	ENSP00000386607.1
VSTM5	ENST00000414919.2	n.1039G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

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

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.380G>A (p.G127E) alteration is located in exon 2 (coding exon 2) of the VSTM5 gene. This alteration results from a G to A substitution at nucleotide position 380, causing the glycine (G) at amino acid position 127 to be replaced by a glutamic acid (E). 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	0.59
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.025	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.48		Loss of sheet (P = 0.0457);
MVP		0.32
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.59
gMVP		0.67

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: chr11-93554201;