chrX-13807680-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001995.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPM6B	NM_001001995.3	MANE Select	c.151G>T	p.Gly51Trp	missense	Exon 2 of 8	NP_001001995.1	Q13491-4
	GPM6B	NM_001001996.3		c.151G>T	p.Gly51Trp	missense	Exon 2 of 8	NP_001001996.1	Q13491-3
	GPM6B	NM_001318729.2		c.5-21872G>T		intron	N/A	NP_001305658.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPM6B	ENST00000316715.9	TSL:2 MANE Select	c.151G>T	p.Gly51Trp	missense	Exon 2 of 8	ENSP00000316861.4	Q13491-4
	GPM6B	ENST00000355135.6	TSL:1	c.151G>T	p.Gly51Trp	missense	Exon 2 of 8	ENSP00000347258.2	Q13491-3
	GPM6B	ENST00000356942.9	TSL:1	c.61+9164G>T		intron	N/A	ENSP00000349420.5	Q13491-1

Frequencies

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

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

African (AFR) AF: 0.0000650 AC: 2 AN: 30780

American (AMR) AF: 0.00 AC: 0 AN: 10629

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3572

South Asian (SAS) AF: 0.00 AC: 0 AN: 2682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6053

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53205

Other (OTH) AF: 0.00 AC: 0 AN: 1506

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
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
M_CAP	Pathogenic	0.87	D
MetaRNN	Benign	0.37	T
MetaSVM	Uncertain	0.59	D
PhyloP100		3.3
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.24	N
REVEL	Uncertain	0.40
Sift	Benign	0.050	D
Sift4G	Uncertain	0.032	D
Polyphen		0.88	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
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs1244158589; hg19: chrX-13825799;