3-119469830-G-C

Position:

chr3-119469830-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_152305.3(POGLUT1):c.96G>C(p.Trp32Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000132 in 1,590,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

POGLUT1
NM_152305.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.11

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 links:

POGLUT1 (HGNC:):

POGLUT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.785

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POGLUT1	NM_152305.3 linkuse as main transcript	c.96G>C	p.Trp32Cys	missense_variant	2/11	ENST00000295588.9	NP_689518.1	Q8NBL1
POGLUT1	NR_024265.2 linkuse as main transcript	n.155G>C		non_coding_transcript_exon_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POGLUT1	ENST00000295588.9 linkuse as main transcript	c.96G>C	p.Trp32Cys	missense_variant	2/11	1	NM_152305.3	ENSP00000295588.4		Q8NBL1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000139

AC:

AN:

1438564

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

717224

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:

0.0000183

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 04, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). This variant has not been reported in the literature in individuals affected with POGLUT1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 32 of the POGLUT1 protein (p.Trp32Cys). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Uncertain

0.077

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.55

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.024

MetaRNN

Pathogenic

0.79

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-5.7

REVEL

Uncertain

0.32

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.028

Polyphen

1.0

Vest4

0.88

MutPred

0.57

Loss of MoRF binding (P = 0.011);

MVP

0.56

MPC

1.5

ClinPred

0.99

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.83

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.37

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.37

Position offset: 27

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over