NM_001001995.3:c.151G>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001001995.3(GPM6B):​c.151G>A​(p.Gly51Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,091,118 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000012 (0 hom. 3 hem.)
• Consequence: GPM6B NM_001001995.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24572143).
• BS2: High Hemizygotes in GnomAdExome4 at 3 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>A	p.Gly51Arg	missense	Exon 2 of 8	NP_001001995.1	Q13491-4
	GPM6B	NM_001001996.3		c.151G>A	p.Gly51Arg	missense	Exon 2 of 8	NP_001001996.1	Q13491-3
	GPM6B	NM_001318729.2		c.5-21872G>A		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>A	p.Gly51Arg	missense	Exon 2 of 8	ENSP00000316861.4	Q13491-4
	GPM6B	ENST00000355135.6	TSL:1	c.151G>A	p.Gly51Arg	missense	Exon 2 of 8	ENSP00000347258.2	Q13491-3
	GPM6B	ENST00000356942.9	TSL:1	c.61+9164G>A		intron	N/A	ENSP00000349420.5	Q13491-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.0000119 AC: 13 AN: 1091118 Hom.: 0 Cov.: 27 AF XY: 0.00000840 AC XY: 3 AN XY: 356984

African (AFR) AF: 0.00 AC: 0 AN: 26309

American (AMR) AF: 0.00 AC: 0 AN: 35103

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19271

East Asian (EAS) AF: 0.00 AC: 0 AN: 30148

South Asian (SAS) AF: 0.00 AC: 0 AN: 53208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4095

European-Non Finnish (NFE) AF: 0.0000155 AC: 13 AN: 836772

Other (OTH) AF: 0.00 AC: 0 AN: 45804

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Benign	0.97
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.77	T
M_CAP	Pathogenic	0.66	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.32	D
PhyloP100		3.3
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.020	N
REVEL	Uncertain	0.35
Sift	Benign	0.31	T
Sift4G	Benign	0.99	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.30		Loss of loop (P = 0.0203)
MVP		0.77
MPC		0.89
ClinPred		0.90	D
GERP RS		4.9
gMVP		0.63
Mutation Taster		=95/5	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;