rs6633380

chrX-13828059-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	UniProt
GPM6B	NM_001001994.3	c.5-42251A>G		intron_variant
GPM6B	NM_001318729.2	c.5-42251A>G		intron_variant
GPM6B	XM_011545497.3	c.5-20290A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPM6B	ENST00000454189.7	c.5-42251A>G		intron_variant		1		A1
GPM6B	ENST00000398361.7	c.-197-42251A>G		intron_variant		2
GPM6B	ENST00000468080.1	c.-197-42251A>G		intron_variant		4
GPM6B	ENST00000493085.5	c.-197-42251A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.278 AC: 30588 AN: 110143 Hom.: 3302 Cov.: 21 AF XY: 0.281 AC XY: 9104 AN XY: 32437

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

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.275

Alfa AF: 0.272 Hom.: 8897

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6633380; hg19: chrX-13846178;