3-119469366-G-T

Position:

• chr3-119469366-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152305.3(POGLUT1):​c.85+260G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 580,154 control chromosomes in the GnomAD database, including 1,030 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (232 hom., cov: 33)
  • Exomes 𝑓: 0.056 (798 hom.)
• Consequence: POGLUT1 NM_152305.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.907

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-119469366-G-T is Benign according to our data. Variant chr3-119469366-G-T is described in ClinVar as [Benign]. Clinvar id is 1277643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POGLUT1	NM_152305.3	c.85+260G>T		intron_variant		ENST00000295588.9	NP_689518.1
POGLUT1	NR_024265.2	n.144+260G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POGLUT1	ENST00000295588.9	c.85+260G>T		intron_variant		1	NM_152305.3	ENSP00000295588.4

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 7165 AN: 152230 Hom.: 232 Cov.: 33

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0503

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.0674

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0478

GnomAD4 exome AF: 0.0565 AC: 24168 AN: 427806 Hom.: 798 AF XY: 0.0559 AC XY: 12612 AN XY: 225506

Gnomad4 AFR exome AF: 0.0141

Gnomad4 AMR exome AF: 0.0438

Gnomad4 ASJ exome AF: 0.0668

Gnomad4 EAS exome AF: 0.0000348

Gnomad4 SAS exome AF: 0.0494

Gnomad4 FIN exome AF: 0.0652

Gnomad4 NFE exome AF: 0.0652

Gnomad4 OTH exome AF: 0.0545

GnomAD4 genome AF: 0.0470 AC: 7159 AN: 152348 Hom.: 232 Cov.: 33 AF XY: 0.0469 AC XY: 3495 AN XY: 74496

Gnomad4 AFR AF: 0.0125

Gnomad4 AMR AF: 0.0502

Gnomad4 ASJ AF: 0.0620

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0507

Gnomad4 FIN AF: 0.0674

Gnomad4 NFE AF: 0.0668

Gnomad4 OTH AF: 0.0468

Alfa AF: 0.0578 Hom.: 29

Bravo AF: 0.0439

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs75416321; hg19: chr3-119188213;