X-13783381-C-T
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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
NM_001001995.3 missense
Scores
12
4
1
Clinical Significance
Conservation
PhyloP100: 4.67
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]
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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 |
---|---|---|---|---|---|---|---|---|
GPM6B | NM_001001995.3 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
GPM6B | ENST00000316715.9 | c.509G>A | p.Arg170Gln | missense_variant | 4/8 | 2 | NM_001001995.3 | ENSP00000316861 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000446 AC: 5AN: 112141Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34295
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GnomAD3 exomes AF: 0.0000314 AC: 5AN: 159345Hom.: 0 AF XY: 0.0000415 AC XY: 2AN XY: 48227
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GnomAD4 exome AF: 0.0000483 AC: 52AN: 1076543Hom.: 0 Cov.: 28 AF XY: 0.0000721 AC XY: 25AN XY: 346799
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GnomAD4 genome AF: 0.0000446 AC: 5AN: 112141Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34295
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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 submitter | clinical testing | Ambry Genetics | Dec 18, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
.;.;.;.;D;.;D;D
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
.;.;.;.;M;.;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Uncertain
D;D;D;D;D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;.;.
Polyphen
1.0
.;D;D;D;D;.;.;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -16
Find out detailed SpliceAI scores and Pangolin per-transcript scores at