3-119486893-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_152305.3(POGLUT1):​c.699T>G​(p.Asp233Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

POGLUT1
NM_152305.3 missense

Scores

2
11
6

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.53
Variant links:
Genes affected
POGLUT1 (HGNC:22954): (protein O-glucosyltransferase 1) This gene encodes a protein with both O-glucosyltransferase and O-xylosyltransferase activity which localizes to the lumen of the endoplasmic reticulum. This protein has a carboxy-terminal KTEL motif which is predicted to function as an endoplasmic reticulum retention signal. This gene is an essential regulator of Notch signalling and likely plays a role in cell fate and tissue formation during development. It may also play a role in the pathogenesis of leukemia. Mutations in this gene have been associated with the autosomal dominant genodermatosis Dowling-Degos disease 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.879
PP5
Variant 3-119486893-T-G is Pathogenic according to our data. Variant chr3-119486893-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 372263.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-119486893-T-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POGLUT1NM_152305.3 linkc.699T>G p.Asp233Glu missense_variant Exon 7 of 11 ENST00000295588.9 NP_689518.1 Q8NBL1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POGLUT1ENST00000295588.9 linkc.699T>G p.Asp233Glu missense_variant Exon 7 of 11 1 NM_152305.3 ENSP00000295588.4 Q8NBL1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2R1 Pathogenic:1
Oct 04, 2022
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.42
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.030
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.30
T
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.0098
T
MetaRNN
Pathogenic
0.88
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
M
PrimateAI
Uncertain
0.67
T
PROVEAN
Uncertain
-3.1
D
REVEL
Uncertain
0.35
Sift
Benign
0.099
T
Sift4G
Benign
0.14
T
Polyphen
0.97
D
Vest4
0.94
MutPred
0.75
Gain of glycosylation at Y236 (P = 0.003);
MVP
0.59
MPC
1.1
ClinPred
0.96
D
GERP RS
3.0
Varity_R
0.63
gMVP
0.87

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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: rs550944082; hg19: chr3-119205740; API