rs3865014

Positions:

• chr15-69269179-G-A
• chr15-69269179-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015554.3(GLCE):​c.1789G>A​(p.Val597Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 1,613,214 control chromosomes in the GnomAD database, including 461,260 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.69 (37255 hom., cov: 31)
  • Exomes 𝑓: 0.76 (424005 hom.)
• Consequence: GLCE NM_015554.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.2591915E-7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLCE	NM_015554.3	c.1789G>A	p.Val597Ile	missense_variant	5/5	ENST00000261858.7	NP_056369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLCE	ENST00000261858.7	c.1789G>A	p.Val597Ile	missense_variant	5/5	1	NM_015554.3	ENSP00000261858.2
GLCE	ENST00000559420.2	c.1597G>A	p.Val533Ile	missense_variant	3/3	1		ENSP00000454092.1

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104655 AN: 151878 Hom.: 37251 Cov.: 31

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.713

GnomAD3 exomes AF: 0.746 AC: 187609 AN: 251324 Hom.: 70846 AF XY: 0.746 AC XY: 101395 AN XY: 135834

Gnomad AFR exome AF: 0.483

Gnomad AMR exome AF: 0.821

Gnomad ASJ exome AF: 0.741

Gnomad EAS exome AF: 0.745

Gnomad SAS exome AF: 0.679

Gnomad FIN exome AF: 0.774

Gnomad NFE exome AF: 0.775

Gnomad OTH exome AF: 0.756

GnomAD4 exome AF: 0.760 AC: 1109861 AN: 1461218 Hom.: 424005 Cov.: 44 AF XY: 0.758 AC XY: 550766 AN XY: 726970

Gnomad4 AFR exome AF: 0.475

Gnomad4 AMR exome AF: 0.812

Gnomad4 ASJ exome AF: 0.745

Gnomad4 EAS exome AF: 0.734

Gnomad4 SAS exome AF: 0.682

Gnomad4 FIN exome AF: 0.775

Gnomad4 NFE exome AF: 0.774

Gnomad4 OTH exome AF: 0.746

GnomAD4 genome AF: 0.689 AC: 104685 AN: 151996 Hom.: 37255 Cov.: 31 AF XY: 0.691 AC XY: 51355 AN XY: 74276

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.772

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.782

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.708

Alfa AF: 0.754 Hom.: 109422

Bravo AF: 0.683

TwinsUK AF: 0.754 AC: 2795

ALSPAC AF: 0.765 AC: 2950

ESP6500AA AF: 0.491 AC: 2162

ESP6500EA AF: 0.766 AC: 6588

ExAC AF: 0.738 AC: 89568

Asia WGS AF: 0.664 AC: 2310 AN: 3478

EpiCase AF: 0.768

EpiControl AF: 0.777

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.023
DANN	Benign	0.23
DEOGEN2	Benign	0.22	T;T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.051	T;T
MetaRNN	Benign	9.3e-7	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.13	N;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.32	N;N
REVEL	Benign	0.027
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.040
MPC		0.32
ClinPred		0.000012	T
GERP RS		-3.2
Varity_R		0.068
gMVP		0.12

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

Other links and lift over

dbSNP: rs3865014; hg19: chr15-69561518; COSMIC: COSV55944915; COSMIC: COSV55944915;