rs6633380

Variant names:

• chrX-13828059-T-C
• rs6633380
• ENST00000454189.7:c.5-42251A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000454189.7(GPM6B):​c.5-42251A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 110,199 control chromosomes in the GnomAD database, including 3,310 homozygotes. There are 9,126 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.

• Frequency: Genomes: 𝑓 0.28 (3310 hom., 9126 hem., cov: 21)
• Consequence: GPM6B ENST00000454189.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPM6B	NM_001318729.2	c.5-42251A>G		intron_variant	Intron 1 of 6		NP_001305658.1
GPM6B	NM_001001994.3	c.5-42251A>G		intron_variant	Intron 1 of 6		NP_001001994.1
GPM6B	XM_011545497.3	c.5-20290A>G		intron_variant	Intron 1 of 7		XP_011543799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPM6B	ENST00000454189.7	c.5-42251A>G		intron_variant	Intron 1 of 6	1		ENSP00000389915.2
GPM6B	ENST00000398361.7	c.-197-42251A>G		intron_variant	Intron 1 of 6	2		ENSP00000381402.3
GPM6B	ENST00000493085.5	c.-197-42251A>G		intron_variant	Intron 1 of 3	3		ENSP00000418199.1
GPM6B	ENST00000468080.1	c.-197-42251A>G		intron_variant	Intron 1 of 3	4		ENSP00000419779.1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 30588 AN: 110143 Hom.: 3302 Cov.: 21

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.195

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.272

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.278 AC: 30617 AN: 110199 Hom.: 3310 Cov.: 21 AF XY: 0.281 AC XY: 9126 AN XY: 32503

African (AFR) AF: 0.269 AC: 8155 AN: 30305

American (AMR) AF: 0.494 AC: 5093 AN: 10313

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 646 AN: 2624

East Asian (EAS) AF: 0.430 AC: 1489 AN: 3461

South Asian (SAS) AF: 0.439 AC: 1112 AN: 2532

European-Finnish (FIN) AF: 0.247 AC: 1440 AN: 5823

Middle Eastern (MID) AF: 0.213 AC: 46 AN: 216

European-Non Finnish (NFE) AF: 0.228 AC: 12043 AN: 52747

Other (OTH) AF: 0.275 AC: 413 AN: 1502

Alfa AF: 0.274 Hom.: 12602

Bravo AF: 0.303

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.56
PhyloP100		0.054
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6633380; hg19: chrX-13846178;