Variant X-13776244-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001001995.3(GPM6B):c.831T>C(p.Ile277=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 1,206,763 control chromosomes in the GnomAD database, including 107 homozygotes. There are 1,176 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 47 hom., 577 hem., cov: 24)

Exomes 𝑓: 0.0022 ( 60 hom. 599 hem. )

Consequence

GPM6B
NM_001001995.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.242

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:

OFD1 (HGNC:2567): (OFD1 centriole and centriolar satellite protein) This gene is located on the X chromosome and encodes a centrosomal protein. A knockout mouse model has been used to study the effect of mutations in this gene. The mouse gene is also located on the X chromosome, however, unlike the human gene it is not subject to X inactivation. Mutations in this gene are associated with oral-facial-digital syndrome type I and Simpson-Golabi-Behmel syndrome type 2. Many pseudogenes have been identified; a single pseudogene is found on chromosome 5 while as many as fifteen have been found on the Y chromosome. [provided by RefSeq, Aug 2016]

OFD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant X-13776244-A-G is Benign according to our data. Variant chrX-13776244-A-G is described in ClinVar as [Benign]. Clinvar id is 778977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.242 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPM6B	NM_001001995.3 linkuse as main transcript	c.831T>C	p.Ile277=	synonymous_variant	7/8	ENST00000316715.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPM6B	ENST00000316715.9 linkuse as main transcript	c.831T>C	p.Ile277=	synonymous_variant	7/8	2	NM_001001995.3	P3	Q13491-4

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2120

AN:

112047

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

567

AN XY:

34209

show subpopulations

Gnomad AFR

AF:

0.0655

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00753

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00844

Gnomad NFE

AF:

0.000113

Gnomad OTH

AF:

0.0119

GnomAD3 exomes

AF:

0.00554

AC:

1013

AN:

182769

Hom.:

AF XY:

0.00345

AC XY:

232

AN XY:

67261

show subpopulations

Gnomad AFR exome

AF:

0.0663

Gnomad AMR exome

AF:

0.00406

Gnomad ASJ exome

AF:

0.000268

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000209

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00215

AC:

2354

AN:

1094663

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

599

AN XY:

360199

show subpopulations

Gnomad4 AFR exome

AF:

0.0686

Gnomad4 AMR exome

AF:

0.00455

Gnomad4 ASJ exome

AF:

0.000103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000371

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000751

Gnomad4 OTH exome

AF:

0.00655

GnomAD4 genome

AF:

0.0190

AC:

2128

AN:

112100

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

577

AN XY:

34272

show subpopulations

Gnomad4 AFR

AF:

0.0656

Gnomad4 AMR

AF:

0.00752

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000113

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00383

Hom.:

Bravo

AF:

0.0210

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over