Variant 3-119469238-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_152305.3(POGLUT1):c.85+132C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00515 in 711,378 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0053 ( 9 hom. )

Consequence

POGLUT1
NM_152305.3 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.419

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 3-119469238-C-T is Benign according to our data. Variant chr3-119469238-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1325988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00452 (689/152360) while in subpopulation NFE AF= 0.00732 (498/68038). AF 95% confidence interval is 0.00679. There are 3 homozygotes in gnomad4. There are 301 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POGLUT1	NM_152305.3 linkuse as main transcript	c.85+132C>T		intron_variant		ENST00000295588.9	NP_689518.1	Q8NBL1
POGLUT1	NR_024265.2 linkuse as main transcript	n.144+132C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POGLUT1	ENST00000295588.9 linkuse as main transcript	c.85+132C>T		intron_variant		1	NM_152305.3	ENSP00000295588.4		Q8NBL1

Frequencies

GnomAD3 genomes

AF:

0.00453

AC:

689

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00732

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00495

AC:

451

AN:

91084

Hom.:

AF XY:

0.00515

AC XY:

255

AN XY:

49516

show subpopulations

Gnomad AFR exome

AF:

0.00146

Gnomad AMR exome

AF:

0.00517

Gnomad ASJ exome

AF:

0.00132

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00285

Gnomad FIN exome

AF:

0.00220

Gnomad NFE exome

AF:

0.00793

Gnomad OTH exome

AF:

0.00881

GnomAD4 exome

AF:

0.00533

AC:

2977

AN:

559018

Hom.:

Cov.:

AF XY:

0.00521

AC XY:

1547

AN XY:

297102

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.00550

Gnomad4 ASJ exome

AF:

0.000874

Gnomad4 EAS exome

AF:

0.0000319

Gnomad4 SAS exome

AF:

0.00295

Gnomad4 FIN exome

AF:

0.00156

Gnomad4 NFE exome

AF:

0.00699

Gnomad4 OTH exome

AF:

0.00472

GnomAD4 genome

AF:

0.00452

AC:

689

AN:

152360

Hom.:

Cov.:

AF XY:

0.00404

AC XY:

301

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00192

Gnomad4 AMR

AF:

0.00516

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00310

Gnomad4 FIN

AF:

0.00103

Gnomad4 NFE

AF:

0.00732

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00575

Hom.:

Bravo

AF:

0.00496

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	POGLUT1: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 22, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.3

DANN

Benign

0.81

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

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