NM_001001995.3:c.641C>T

Variant names:

• chrX-13779874-G-A
• rs200352293
• NM_001001995.3:c.641C>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.641C>T​(p.Pro214Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000284 in 1,197,963 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000028 (0 hom. 12 hem.)
• Consequence: GPM6B NM_001001995.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.81
• 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=0.31754547).
• BS2: High Hemizygotes in GnomAdExome4 at 12 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.641C>T	p.Pro214Leu	missense	Exon 5 of 8	NP_001001995.1	Q13491-4
	GPM6B	NM_001001996.3		c.641C>T	p.Pro214Leu	missense	Exon 5 of 8	NP_001001996.1	Q13491-3
	GPM6B	NM_001318729.2		c.464C>T	p.Pro155Leu	missense	Exon 4 of 7	NP_001305658.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPM6B	ENST00000316715.9	TSL:2 MANE Select	c.641C>T	p.Pro214Leu	missense	Exon 5 of 8	ENSP00000316861.4	Q13491-4
	GPM6B	ENST00000355135.6	TSL:1	c.641C>T	p.Pro214Leu	missense	Exon 5 of 8	ENSP00000347258.2	Q13491-3
	GPM6B	ENST00000356942.9	TSL:1	c.521C>T	p.Pro174Leu	missense	Exon 4 of 7	ENSP00000349420.5	Q13491-1

Frequencies

GnomAD3 genomes AF: 0.0000358 AC: 4 AN: 111708 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000652

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: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000110 AC: 2 AN: 182587 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000276 AC: 30 AN: 1086255 Hom.: 0 Cov.: 29 AF XY: 0.0000339 AC XY: 12 AN XY: 354011

African (AFR) AF: 0.00 AC: 0 AN: 26265

American (AMR) AF: 0.00 AC: 0 AN: 35086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19169

East Asian (EAS) AF: 0.00 AC: 0 AN: 29962

South Asian (SAS) AF: 0.000190 AC: 10 AN: 52740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40269

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4090

European-Non Finnish (NFE) AF: 0.0000240 AC: 20 AN: 833161

Other (OTH) AF: 0.00 AC: 0 AN: 45513

GnomAD4 genome AF: 0.0000358 AC: 4 AN: 111708 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33888

African (AFR) AF: 0.0000652 AC: 2 AN: 30654

American (AMR) AF: 0.00 AC: 0 AN: 10560

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3576

South Asian (SAS) AF: 0.00 AC: 0 AN: 2644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53202

Other (OTH) AF: 0.00 AC: 0 AN: 1497

Alfa AF: 0.0000505 Hom.: 4

Bravo AF: 0.0000340

ExAC AF: 0.0000247 AC: 3

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	0.069
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.51	D
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	0.42	D
MutationAssessor	Benign	0.39	N
PhyloP100		4.8
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.41
Sift	Benign	0.27	T
Sift4G	Benign	0.47	T
Polyphen		0.0010	B
Vest4		0.10
MutPred		0.62		Loss of disorder (P = 0.0106)
MVP		0.70
MPC		0.78
ClinPred		0.31	T
GERP RS		4.5
Varity_R		0.10
gMVP		0.90
Mutation Taster		=80/20	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: rs200352293; hg19: chrX-13797993;