rs1005589

chrX-13873228-G-AchrX-13873228-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000454189.7(GPM6B):c.4+65279C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.75 (22883 hom., 23105 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: GPM6B ENST00000454189.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS2: High Homozygotes in GnomAd at 22885 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPM6B	NM_001001994.3	c.4+65279C>T		intron_variant
GPM6B	NM_001318729.2	c.4+65279C>T		intron_variant
GPM6B	XM_011545497.3	c.4+65279C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPM6B	ENST00000454189.7	c.4+65279C>T		intron_variant		1		A1
GPM6B	ENST00000398361.7	c.-198+65099C>T		intron_variant		2
GPM6B	ENST00000468080.1	c.-198+16224C>T		intron_variant		4
GPM6B	ENST00000493085.5	c.-198+15753C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.755 AC: 81744 AN: 108248 Hom.: 22885 Cov.: 21 AF XY: 0.754 AC XY: 23082 AN XY: 30606

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.788

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.755 AC: 81758 AN: 108295 Hom.: 22883 Cov.: 21 AF XY: 0.754 AC XY: 23105 AN XY: 30663

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.775

Gnomad4 ASJ AF: 0.820

Gnomad4 EAS AF: 0.927

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.834

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.789

Alfa AF: 0.825 Hom.: 51991

Bravo AF: 0.747

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.25
Dann	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1005589; hg19: chrX-13891347;