4-175812196-T-G

Position:

• chr4-175812196-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_201591.3(GPM6A):​c.32A>C​(p.Gln11Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPM6A NM_201591.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.04

Genes affected

GPM6A (HGNC:4460): (glycoprotein M6A) Predicted to enable calcium channel activity. Involved in neuron migration and stem cell differentiation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

GPM6A-DT (HGNC:55577): (GPM6A divergent transcript)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39166787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPM6A	NM_201591.3	c.32A>C	p.Gln11Pro	missense_variant	1/7	ENST00000393658.7	NP_963885.1
GPM6A-DT	NR_125901.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPM6A	ENST00000393658.7	c.32A>C	p.Gln11Pro	missense_variant	1/7	1	NM_201591.3	ENSP00000377268	P1
GPM6A-DT	ENST00000514864.1			downstream_gene_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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

Aug 21, 2023

The c.32A>C (p.Q11P) alteration is located in exon 1 (coding exon 1) of the GPM6A gene. This alteration results from a A to C substitution at nucleotide position 32, causing the glutamine (Q) at amino acid position 11 to be replaced by a proline (P). 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	0.098
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.075	T;T;.
Eigen	Benign	-0.061
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.56	.;T;T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Pathogenic	0.80	D
MutationAssessor	Benign	0.34	N;N;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.20	N;N;N
REVEL	Uncertain	0.50
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.095	T;T;T
Polyphen		0.021	B;B;.
Vest4		0.51
MutPred		0.19		Loss of glycosylation at K12 (P = 0.0419);Loss of glycosylation at K12 (P = 0.0419);Loss of glycosylation at K12 (P = 0.0419);
MVP		0.90
MPC		0.76
ClinPred		0.44	T
GERP RS		5.8
Varity_R		0.24
gMVP		0.87

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: chr4-176733347;