15-69269749-A-T

Variant summary

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

The NM_015554.3(GLCE):c.*505A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,890 control chromosomes in the GnomAD database, including 35,548 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.66 (35321 hom., cov: 33)
  • Exomes 𝑓: 0.78 (227 hom.)
• Consequence: GLCE NM_015554.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440

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 (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLCE	NM_015554.3	c.*505A>T		3_prime_UTR_variant	5/5	ENST00000261858.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLCE	ENST00000261858.7	c.*505A>T		3_prime_UTR_variant	5/5	1	NM_015554.3	P1
GLCE	ENST00000559420.2	c.*505A>T		3_prime_UTR_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100288 AN: 152024 Hom.: 35318 Cov.: 33

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.697

GnomAD4 exome AF: 0.779 AC: 583 AN: 748 Hom.: 227 Cov.: 0 AF XY: 0.797 AC XY: 341 AN XY: 428

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.938

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.700

Gnomad4 FIN exome AF: 0.782

Gnomad4 NFE exome AF: 0.797

Gnomad4 OTH exome AF: 0.643

GnomAD4 genome AF: 0.659 AC: 100321 AN: 152142 Hom.: 35321 Cov.: 33 AF XY: 0.663 AC XY: 49282 AN XY: 74376

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.747

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.783

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.691

Alfa AF: 0.706 Hom.: 4880

Bravo AF: 0.648

Asia WGS AF: 0.661 AC: 2292 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	5.4
Dann	Benign	0.82

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: rs3205721; hg19: chr15-69562088;