dbSNP rs5979998: GPM6B:c.4+22593C>T (chrX-13915914-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_001318729.2(GPM6B):c.4+22593C>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 0.68 ( 18835 hom., 22011 hem., cov: 23)

Failed GnomAD Quality Control

Consequence

GPM6B
NM_001318729.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.449

Variant links:

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]

GPM6B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
GPM6B	NM_001318729.2 link	c.4+22593C>T	intron_variant	Intron 1 of 6	NP_001305658.1	Q59FD5
GPM6B	NM_001001994.3 link	c.4+22593C>T	intron_variant	Intron 1 of 6	NP_001001994.1	Q13491-2
GPM6B	XM_011545497.3 link	c.4+22593C>T	intron_variant	Intron 1 of 7	XP_011543799.1
GPM6B	XM_017029432.2 link	c.4+22593C>T	intron_variant	Intron 1 of 7	XP_016884921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPM6B	ENST00000454189.7 link	c.4+22593C>T		intron_variant	Intron 1 of 6	1		ENSP00000389915.2		Q13491-2
GPM6B	ENST00000398361.7 link	c.-198+22413C>T		intron_variant	Intron 1 of 6	2		ENSP00000381402.3		B7Z248

Frequencies

GnomAD3 genomes

AF:

0.685

AC:

75617

AN:

110429

Hom.:

18842

Cov.:

AF XY:

0.672

AC XY:

21959

AN XY:

32667

show subpopulations

Gnomad AFR

AF:

0.701

Gnomad AMI

AF:

0.815

Gnomad AMR

AF:

0.556

Gnomad ASJ

AF:

0.722

Gnomad EAS

AF:

0.332

Gnomad SAS

AF:

0.495

Gnomad FIN

AF:

0.719

Gnomad MID

AF:

0.647

Gnomad NFE

AF:

0.727

Gnomad OTH

AF:

0.659

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:

0.685

AC:

75655

AN:

110480

Hom.:

18835

Cov.:

AF XY:

0.673

AC XY:

22011

AN XY:

32728

show subpopulations

Gnomad4 AFR

AF:

0.701

Gnomad4 AMR

AF:

0.556

Gnomad4 ASJ

AF:

0.722

Gnomad4 EAS

AF:

0.332

Gnomad4 SAS

AF:

0.494

Gnomad4 FIN

AF:

0.719

Gnomad4 NFE

AF:

0.727

Gnomad4 OTH

AF:

0.656

Alfa

AF:

0.699

Hom.:

7692

Bravo

AF:

0.669

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

2.1

DANN

Benign

0.45

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over