NM_152305.3:c.85+20G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_152305.3(POGLUT1):​c.85+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

POGLUT1
NM_152305.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00100

Publications

0 publications found
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]
POGLUT1 Gene-Disease associations (from GenCC):
  • autosomal recessive limb-girdle muscular dystrophy
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • Dowling-Degos disease 4
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
  • autosomal recessive limb-girdle muscular dystrophy type 2R1
    Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • Dowling-Degos disease
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 3-119469126-G-A is Benign according to our data. Variant chr3-119469126-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3009104.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POGLUT1NM_152305.3 linkc.85+20G>A intron_variant Intron 1 of 10 ENST00000295588.9 NP_689518.1 Q8NBL1
POGLUT1NR_024265.2 linkn.144+20G>A intron_variant Intron 1 of 10

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POGLUT1ENST00000295588.9 linkc.85+20G>A intron_variant Intron 1 of 10 1 NM_152305.3 ENSP00000295588.4 Q8NBL1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1420472
Hom.:
0
Cov.:
27
AF XY:
0.00
AC XY:
0
AN XY:
706414
African (AFR)
AF:
0.00
AC:
0
AN:
32492
American (AMR)
AF:
0.00
AC:
0
AN:
41940
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25672
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38208
South Asian (SAS)
AF:
0.00
AC:
0
AN:
83042
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
46232
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4876
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1089150
Other (OTH)
AF:
0.00
AC:
0
AN:
58860
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not provided Benign:1
Oct 30, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
8.2
DANN
Benign
0.78
PhyloP100
0.0010
PromoterAI
0.040
Neutral

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

Other links and lift over

dbSNP: rs75388849; hg19: chr3-119187973; API