rs5978663

Positions:

• chrX-13785841-C-A
• chrX-13785841-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001001995.3(GPM6B):​c.182-33G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000441 in 1,134,024 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 0.000027 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.0000020 (0 hom. 1 hem.)
• Consequence: GPM6B NM_001001995.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.783

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPM6B	NM_001001995.3	c.182-33G>T		intron_variant		ENST00000316715.9	NP_001001995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPM6B	ENST00000316715.9	c.182-33G>T		intron_variant		2	NM_001001995.3	ENSP00000316861	P3

Frequencies

GnomAD3 genomes AF: 0.0000272 AC: 3 AN: 110314 Hom.: 0 Cov.: 23 AF XY: 0.0000307 AC XY: 1 AN XY: 32542

Gnomad AFR AF: 0.0000661

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000961

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: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000653 AC: 1 AN: 153076 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 42962

Gnomad AFR exome AF: 0.0000835

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.00000195 AC: 2 AN: 1023710 Hom.: 0 Cov.: 19 AF XY: 0.00000332 AC XY: 1 AN XY: 301568

Gnomad4 AFR exome AF: 0.0000804

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000272 AC: 3 AN: 110314 Hom.: 0 Cov.: 23 AF XY: 0.0000307 AC XY: 1 AN XY: 32542

Gnomad4 AFR AF: 0.0000661

Gnomad4 AMR AF: 0.0000961

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.0030
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs5978663; hg19: chrX-13803960;