rs371232341

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024089.3(POGLUT2):​c.1459G>T​(p.Asp487Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,470 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D487N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

POGLUT2
NM_024089.3 missense

Scores

4
6
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.37
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POGLUT2NM_024089.3 linkc.1459G>T p.Asp487Tyr missense_variant Exon 9 of 10 ENST00000376004.5 NP_076994.2 Q6UW63
POGLUT2NM_001318732.2 linkc.802G>T p.Asp268Tyr missense_variant Exon 10 of 11 NP_001305661.1 Q6UW63
POGLUT2XM_047430604.1 linkc.802G>T p.Asp268Tyr missense_variant Exon 7 of 8 XP_047286560.1
POGLUT2XM_005254075.4 linkc.1383+1570G>T intron_variant Intron 8 of 8 XP_005254132.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POGLUT2ENST00000376004.5 linkc.1459G>T p.Asp487Tyr missense_variant Exon 9 of 10 1 NM_024089.3 ENSP00000365172.4 Q6UW63

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251426
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135886
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461274
Hom.:
0
Cov.:
29
AF XY:
0.00000413
AC XY:
3
AN XY:
726992
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.017
T
Eigen
Pathogenic
0.83
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.031
D
MetaRNN
Uncertain
0.74
D
MetaSVM
Benign
-0.96
T
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-2.3
N
REVEL
Benign
0.28
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.016
D
Polyphen
1.0
D
Vest4
0.83
MutPred
0.49
Loss of disorder (P = 0.0065);
MVP
0.42
MPC
0.62
ClinPred
0.88
D
GERP RS
5.7
Varity_R
0.36
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.31
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.31
Position offset: -32

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.

Other links and lift over

dbSNP: rs371232341; hg19: chr13-103438614; API