chr13-102791085-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024089.3(POGLUT2):​c.899G>A​(p.Ser300Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

POGLUT2
NM_024089.3 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.37
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.070080906).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POGLUT2NM_024089.3 linkc.899G>A p.Ser300Asn missense_variant Exon 6 of 10 ENST00000376004.5 NP_076994.2 Q6UW63
POGLUT2NM_001318732.2 linkc.242G>A p.Ser81Asn missense_variant Exon 7 of 11 NP_001305661.1 Q6UW63
POGLUT2XM_005254075.4 linkc.899G>A p.Ser300Asn missense_variant Exon 6 of 9 XP_005254132.1
POGLUT2XM_047430604.1 linkc.242G>A p.Ser81Asn missense_variant Exon 4 of 8 XP_047286560.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POGLUT2ENST00000376004.5 linkc.899G>A p.Ser300Asn missense_variant Exon 6 of 10 1 NM_024089.3 ENSP00000365172.4 Q6UW63

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251452
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461878
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 29, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.899G>A (p.S300N) alteration is located in exon 6 (coding exon 6) of the KDELC1 gene. This alteration results from a G to A substitution at nucleotide position 899, causing the serine (S) at amino acid position 300 to be replaced by an asparagine (N). 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
0.060
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
16
DANN
Benign
0.24
DEOGEN2
Benign
0.0064
T
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.36
FATHMM_MKL
Benign
0.63
D
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.070
T
MetaSVM
Benign
-0.96
T
PrimateAI
Benign
0.41
T
PROVEAN
Benign
1.8
N
REVEL
Benign
0.070
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.19
MutPred
0.22
Loss of catalytic residue at K301 (P = 0.0918);
MVP
0.17
MPC
0.11
ClinPred
0.067
T
GERP RS
2.3
Varity_R
0.032
gMVP
0.32

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1340299638; hg19: chr13-103443435; API