X-13807680-C-A

Variant names:

• chrX-13807680-C-A
• rs1244158589
• NM_001001995.3:c.151G>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001001995.3(GPM6B):​c.151G>T​(p.Gly51Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 111,996 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G51R) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.000018 (0 hom., 2 hem., cov: 23)
• Consequence: GPM6B NM_001001995.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.29

Genes affected

GPM6B (HGNC:4461): (glycoprotein M6B) This gene encodes a membrane glycoprotein that belongs to the proteolipid protein family. Proteolipid protein family members are expressed in most brain regions and are thought to be involved in cellular housekeeping functions such as membrane trafficking and cell-to-cell communication. This protein may also be involved in osteoblast differentiation. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are located on chromosomes Y and 22. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.37028655).
• BS2: High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPM6B	NM_001001995.3	c.151G>T	p.Gly51Trp	missense_variant	Exon 2 of 8	ENST00000316715.9	NP_001001995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPM6B	ENST00000316715.9	c.151G>T	p.Gly51Trp	missense_variant	Exon 2 of 8	2	NM_001001995.3	ENSP00000316861.4

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111996 Hom.: 0 Cov.: 23 AF XY: 0.0000586 AC XY: 2 AN XY: 34150

Gnomad AFR AF: 0.0000650

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome Cov.: 27

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111996 Hom.: 0 Cov.: 23 AF XY: 0.0000586 AC XY: 2 AN XY: 34150

Gnomad4 AFR AF: 0.0000650

Gnomad4 AMR AF: 0.00

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

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	0.99
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Pathogenic	0.87	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Uncertain	0.59	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.24	N;N;N
REVEL	Uncertain	0.40
Sift	Benign	0.050	D;T;T
Sift4G	Uncertain	0.032	D;D;D
Polyphen		0.88, 0.92	.;P;P
Vest4		0.37
MutPred		0.36		.;Loss of disorder (P = 0.0055);.;
MVP		0.73
MPC		1.3
ClinPred		0.97	D
GERP RS		4.9
gMVP		0.70

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

Other links and lift over

dbSNP: rs1244158589; hg19: chrX-13825799;