chr13-102789016-T-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024089.3(POGLUT2):c.1289A>C(p.Glu430Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,460,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E430G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

POGLUT2
NM_024089.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.16

Publications

1 publications found

Variant links:

Genes affected

POGLUT2 (HGNC:19350): (protein O-glucosyltransferase 2) This gene encodes a protein product localized to the lumen of the endoplasmic reticulum. As a member of the endoplasmic reticulum protein family the encoded protein contains a Lys-Asp-Glu-Leu or KDEL motif located at the extreme C-terminus which prevents all endoplasmic reticulum resident proteins from being secreted. Proteins carrying this motif are bound by a receptor in the Golgi apparatus so that the receptor-ligand complex returns to the endoplasmic reticulum. A processed non-transcribed pseudogene located in an intron of a sodium transporter gene on chromosome 5 has been defined for this gene. This gene has multiple transcript variants which are predicted to encode distinct isoforms. [provided by RefSeq, Jan 2016]

POGLUT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1361691).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POGLUT2	NM_024089.3 link	c.1289A>C	p.Glu430Ala	missense_variant	Exon 7 of 10	ENST00000376004.5	NP_076994.2	Q6UW63
POGLUT2	NM_001439010.1 link	c.1289A>C	p.Glu430Ala	missense_variant	Exon 7 of 9		NP_001425939.1
POGLUT2	NM_001318732.2 link	c.632A>C	p.Glu211Ala	missense_variant	Exon 8 of 11		NP_001305661.1	Q6UW63
POGLUT2	XM_047430604.1 link	c.632A>C	p.Glu211Ala	missense_variant	Exon 5 of 8		XP_047286560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POGLUT2	ENST00000376004.5 link	c.1289A>C	p.Glu430Ala	missense_variant	Exon 7 of 10	1	NM_024089.3	ENSP00000365172.4		Q6UW63

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000518

AC:

AN:

251108

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1460802

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726764

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33444

American (AMR)

AF:

0.000268

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5466

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1111372

Other (OTH)

AF:

0.00

AC:

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 18, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1289A>C (p.E430A) alteration is located in exon 7 (coding exon 7) of the KDELC1 gene. This alteration results from a A to C substitution at nucleotide position 1289, causing the glutamic acid (E) at amino acid position 430 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.094

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.0072

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.73

M_CAP

Benign

0.0053

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

PhyloP100

4.2

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.047

Sift

Benign

0.14

Sift4G

Benign

0.29

Polyphen

0.0010

Vest4

0.41

MVP

0.35

MPC

0.13

ClinPred

0.10

GERP RS

4.5

Varity_R

0.13

gMVP

0.67

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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chr13-102789016-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over