X-13783381-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001001995.3(GPM6B):​c.509G>A​(p.Arg170Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000048 in 1,188,684 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.000048 ( 0 hom. 25 hem. )

Consequence

GPM6B
NM_001001995.3 missense

Scores

12
4
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.67
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.876
BS2
High Hemizygotes in GnomAdExome4 at 25 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GPM6BNM_001001995.3 linkuse as main transcriptc.509G>A p.Arg170Gln missense_variant 4/8 ENST00000316715.9 NP_001001995.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GPM6BENST00000316715.9 linkuse as main transcriptc.509G>A p.Arg170Gln missense_variant 4/82 NM_001001995.3 ENSP00000316861 P3Q13491-4

Frequencies

GnomAD3 genomes
AF:
0.0000446
AC:
5
AN:
112141
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34295
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000939
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000314
AC:
5
AN:
159345
Hom.:
0
AF XY:
0.0000415
AC XY:
2
AN XY:
48227
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000169
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000546
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000483
AC:
52
AN:
1076543
Hom.:
0
Cov.:
28
AF XY:
0.0000721
AC XY:
25
AN XY:
346799
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.0000613
Gnomad4 OTH exome
AF:
0.0000221
GnomAD4 genome
AF:
0.0000446
AC:
5
AN:
112141
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34295
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000939
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000416
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000412
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 18, 2023The c.509G>A (p.R170Q) alteration is located in exon 4 (coding exon 4) of the GPM6B gene. This alteration results from a G to A substitution at nucleotide position 509, causing the arginine (R) at amino acid position 170 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.71
BayesDel_addAF
Pathogenic
0.54
D
BayesDel_noAF
Pathogenic
0.70
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Pathogenic
0.86
.;.;.;.;D;.;D;D
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.91
D;D;D;D;D;D;D;D
M_CAP
Pathogenic
0.98
D
MetaRNN
Pathogenic
0.88
D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
2.9
.;.;.;.;M;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-2.7
D;D;D;D;D;D;D;D
REVEL
Pathogenic
0.94
Sift
Uncertain
0.012
D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.018
D;D;D;D;D;D;.;.
Polyphen
1.0
.;D;D;D;D;.;.;.
Vest4
0.84
MVP
0.71
MPC
1.0
ClinPred
0.79
D
GERP RS
5.2
Varity_R
0.72
gMVP
0.98

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.28
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.28
Position offset: -16

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: rs770553728; hg19: chrX-13801500; API