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GeneBe

X-13777400-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001001995.3(GPM6B):c.723C>T(p.Pro241=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000065 in 1,199,891 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 4 hem., cov: 23)
Exomes 𝑓: 0.000058 ( 0 hom. 20 hem. )

Consequence

GPM6B
NM_001001995.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.68
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-13777400-G-A is Benign according to our data. Variant chrX-13777400-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2660034.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.68 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Hemizygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GPM6BNM_001001995.3 linkuse as main transcriptc.723C>T p.Pro241= synonymous_variant 6/8 ENST00000316715.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GPM6BENST00000316715.9 linkuse as main transcriptc.723C>T p.Pro241= synonymous_variant 6/82 NM_001001995.3 P3Q13491-4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000134
AC:
15
AN:
111663
Hom.:
0
Cov.:
23
AF XY:
0.000118
AC XY:
4
AN XY:
33895
show subpopulations
Gnomad AFR
AF:
0.000228
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000758
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000113
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000131
AC:
24
AN:
183163
Hom.:
0
AF XY:
0.0000739
AC XY:
5
AN XY:
67663
show subpopulations
Gnomad AFR exome
AF:
0.000380
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000669
Gnomad EAS exome
AF:
0.0000722
Gnomad SAS exome
AF:
0.000367
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000490
Gnomad OTH exome
AF:
0.000443
GnomAD4 exome
AF:
0.0000579
AC:
63
AN:
1088228
Hom.:
0
Cov.:
27
AF XY:
0.0000565
AC XY:
20
AN XY:
354154
show subpopulations
Gnomad4 AFR exome
AF:
0.000152
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000518
Gnomad4 EAS exome
AF:
0.0000332
Gnomad4 SAS exome
AF:
0.000130
Gnomad4 FIN exome
AF:
0.0000494
Gnomad4 NFE exome
AF:
0.0000408
Gnomad4 OTH exome
AF:
0.000109
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000134
AC:
15
AN:
111663
Hom.:
0
Cov.:
23
AF XY:
0.000118
AC XY:
4
AN XY:
33895
show subpopulations
Gnomad4 AFR
AF:
0.000228
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000758
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000113
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000260
Hom.:
2
Bravo
AF:
0.000125
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2022GPM6B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
Cadd
Benign
0.31
Dann
Benign
0.61

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

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

Other links and lift over

dbSNP: rs141687297; hg19: chrX-13795519; API