Genetic Variant POGLUT1:p.Arg24Leu (chr3-119469092-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_152305.3(POGLUT1):c.71G>T(p.Arg24Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000688 in 1,453,614 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R24H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

POGLUT1
NM_152305.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.33

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

POGLUT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POGLUT1	NM_152305.3 link	c.71G>T	p.Arg24Leu	missense_variant	Exon 1 of 11	ENST00000295588.9	NP_689518.1	Q8NBL1
POGLUT1	NR_024265.2 link	n.130G>T		non_coding_transcript_exon_variant	Exon 1 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POGLUT1	ENST00000295588.9 link	c.71G>T	p.Arg24Leu	missense_variant	Exon 1 of 11	1	NM_152305.3	ENSP00000295588.4		Q8NBL1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000436

AC:

AN:

229198

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000688

AC:

AN:

1453614

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

722964

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33290

American (AMR)

AF:

0.0000226

AC:

AN:

44332

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26012

East Asian (EAS)

AF:

0.00

AC:

AN:

39392

South Asian (SAS)

AF:

0.00

AC:

AN:

85522

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4814

European-Non Finnish (NFE)

AF:

0.00000721

AC:

AN:

1109862

Other (OTH)

AF:

0.0000167

AC:

AN:

59954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.068

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.81

M_CAP

Benign

0.0085

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

4.3

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.37

REVEL

Benign

0.15

Sift

Benign

0.41

Sift4G

Benign

0.38

Polyphen

0.99

Vest4

0.56

MutPred

0.28

Loss of MoRF binding (P = 0.0332);

MVP

0.56

MPC

0.46

ClinPred

0.79

GERP RS

4.9

PromoterAI

0.061

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.23

gMVP

0.57

Mutation Taster

=91/9

polymorphism

(source)

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

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chr3-119469092-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over