chr15-69268747-A-G

Variant summary

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

The NM_015554.3(GLCE):ā€‹c.1357A>Gā€‹(p.Thr453Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000911 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T453I) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.000039 ( 0 hom., cov: 32)
Exomes š‘“: 0.000096 ( 0 hom. )

Consequence

GLCE
NM_015554.3 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.18
Variant links:
Genes affected
GLCE (HGNC:17855): (glucuronic acid epimerase) Enables calcium ion binding activity; heparosan-N-sulfate-glucuronate 5-epimerase activity; and protein homodimerization activity. Involved in heparan sulfate proteoglycan biosynthetic process. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

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/exons MANE UniProt
GLCENM_015554.3 linkuse as main transcriptc.1357A>G p.Thr453Ala missense_variant 5/5 ENST00000261858.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GLCEENST00000261858.7 linkuse as main transcriptc.1357A>G p.Thr453Ala missense_variant 5/51 NM_015554.3 P1
GLCEENST00000559420.2 linkuse as main transcriptc.1165A>G p.Thr389Ala missense_variant 3/31

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152222
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000796
AC:
20
AN:
251388
Hom.:
0
AF XY:
0.0000883
AC XY:
12
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
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:
0.000158
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000965
AC:
141
AN:
1461878
Hom.:
0
Cov.:
32
AF XY:
0.0000935
AC XY:
68
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000447
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:
0.000119
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152222
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000129
Hom.:
0
Bravo
AF:
0.0000491
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.000164
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 10, 2023The c.1357A>G (p.T453A) alteration is located in exon 5 (coding exon 3) of the GLCE gene. This alteration results from a A to G substitution at nucleotide position 1357, causing the threonine (T) at amino acid position 453 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
0.19
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.32
T;T
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Benign
0.80
T;T
M_CAP
Benign
0.015
T
MetaRNN
Uncertain
0.68
D;D
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
2.0
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-1.2
N;N
REVEL
Benign
0.24
Sift
Benign
0.038
D;D
Sift4G
Uncertain
0.047
D;D
Polyphen
0.97
D;.
Vest4
0.61
MVP
0.60
MPC
0.77
ClinPred
0.25
T
GERP RS
5.1
Varity_R
0.43
gMVP
0.78

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: rs199559391; hg19: chr15-69561086; API