Variant 15-69256054-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015554.3(GLCE):c.248A>G(p.Lys83Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00216 in 1,614,056 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 16 hom. )

Consequence

GLCE
NM_015554.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.96

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]

GLCE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002390802).

BP6

Variant 15-69256054-A-G is Benign according to our data. Variant chr15-69256054-A-G is described in ClinVar as [Benign]. Clinvar id is 787120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00999 (1521/152242) while in subpopulation AFR AF= 0.0324 (1344/41542). AF 95% confidence interval is 0.0309. There are 22 homozygotes in gnomad4. There are 719 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLCE	NM_015554.3 linkuse as main transcript	c.248A>G	p.Lys83Arg	missense_variant	3/5	ENST00000261858.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLCE	ENST00000261858.7 linkuse as main transcript	c.248A>G	p.Lys83Arg	missense_variant	3/5	1	NM_015554.3	P1
GLCE	ENST00000559420.2 linkuse as main transcript	c.56A>G	p.Lys19Arg	missense_variant	1/3	1

Frequencies

GnomAD3 genomes

AF:

0.0100

AC:

1521

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00779

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00269

AC:

675

AN:

251128

Hom.:

AF XY:

0.00217

AC XY:

294

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.0311

Gnomad AMR exome

AF:

0.00234

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000529

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00134

AC:

1963

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

882

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0321

Gnomad4 AMR exome

AF:

0.00315

Gnomad4 ASJ exome

AF:

0.000727

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000452

Gnomad4 OTH exome

AF:

0.00283

GnomAD4 genome

AF:

0.00999

AC:

1521

AN:

152242

Hom.:

Cov.:

AF XY:

0.00966

AC XY:

719

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0324

Gnomad4 AMR

AF:

0.00778

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00262

Hom.:

Bravo

AF:

0.0112

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0268

AC:

118

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00315

AC:

382

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

T;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.75

T;T

MetaRNN

Benign

0.0024

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.76

N;.

MutationTaster

Benign

0.70

D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.19

N;N

REVEL

Benign

0.074

Sift

Benign

0.21

T;T

Sift4G

Benign

0.49

T;T

Polyphen

0.0010

B;.

Vest4

0.063

MVP

0.47

MPC

0.32

ClinPred

0.020

GERP RS

3.0

Varity_R

0.13

gMVP

0.39

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over