3-119469238-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.419

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]

ACMG classification

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 GnomAd at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POGLUT1	NM_152305.3	c.85+132C>T		intron_variant		ENST00000295588.9
POGLUT1	NR_024265.2	n.144+132C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POGLUT1	ENST00000295588.9	c.85+132C>T		intron_variant		1	NM_152305.3	P1

Frequencies

GnomAD3 genomes AF: 0.00453 AC: 689 AN: 152242 Hom.: 3 Cov.: 33

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.: 2 AF XY: 0.00515 AC XY: 255 AN XY: 49516

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.: 9 Cov.: 6 AF XY: 0.00521 AC XY: 1547 AN XY: 297102

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.: 3 Cov.: 33 AF XY: 0.00404 AC XY: 301 AN XY: 74508

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.: 1

Bravo AF: 0.00496

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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	- -

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

Other links and lift over

dbSNP: rs530616432; hg19: chr3-119188085;