rs1450952390
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3
The NM_024089.3(POGLUT2):c.1355T>C(p.Ile452Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
POGLUT2
NM_024089.3 missense
NM_024089.3 missense
Scores
4
7
7
Clinical Significance
Conservation
PhyloP100: 9.20
Publications
1 publications found
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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.746
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| POGLUT2 | NM_024089.3 | c.1355T>C | p.Ile452Thr | missense_variant | Exon 8 of 10 | ENST00000376004.5 | NP_076994.2 | |
| POGLUT2 | NM_001439010.1 | c.1355T>C | p.Ile452Thr | missense_variant | Exon 8 of 9 | NP_001425939.1 | ||
| POGLUT2 | NM_001318732.2 | c.698T>C | p.Ile233Thr | missense_variant | Exon 9 of 11 | NP_001305661.1 | ||
| POGLUT2 | XM_047430604.1 | c.698T>C | p.Ile233Thr | missense_variant | Exon 6 of 8 | XP_047286560.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.0000197 AC: 3AN: 152240Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
3
AN:
152240
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1438464Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 712922
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1438464
Hom.:
Cov.:
28
AF XY:
AC XY:
0
AN XY:
712922
African (AFR)
AF:
AC:
0
AN:
33122
American (AMR)
AF:
AC:
0
AN:
43136
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25684
East Asian (EAS)
AF:
AC:
0
AN:
39256
South Asian (SAS)
AF:
AC:
0
AN:
83406
European-Finnish (FIN)
AF:
AC:
0
AN:
52844
Middle Eastern (MID)
AF:
AC:
0
AN:
5678
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1095958
Other (OTH)
AF:
AC:
0
AN:
59380
GnomAD4 genome 0.0000197 AC: 3AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74378 show subpopulations
GnomAD4 genome
AF:
AC:
3
AN:
152240
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74378
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41466
American (AMR)
AF:
AC:
0
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5204
South Asian (SAS)
AF:
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
2
AN:
68044
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.542
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Nov 11, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.1355T>C (p.I452T) alteration is located in exon 8 (coding exon 8) of the KDELC1 gene. This alteration results from a T to C substitution at nucleotide position 1355, causing the isoleucine (I) at amino acid position 452 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of stability (P = 0.0322);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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