rs3865014

Variant names:

• chr15-69269179-G-A
• rs3865014
• NM_015554.3:c.1789G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 41 publications found

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]

PAQR5-DT (HGNC:55353): (PAQR5 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GLCE	NM_015554.3	c.1789G>A	p.Val597Ile	missense_variant	Exon 5 of 5	ENST00000261858.7	NP_056369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLCE	ENST00000261858.7	c.1789G>A	p.Val597Ile	missense_variant	Exon 5 of 5	1	NM_015554.3	ENSP00000261858.2
GLCE	ENST00000559420.2	c.1597G>A	p.Val533Ile	missense_variant	Exon 3 of 3	1		ENSP00000454092.1
PAQR5-DT	ENST00000746778.1	n.446-3746C>T		intron_variant	Intron 2 of 3

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

GnomAD2 exomes AF: 0.746 AC: 187609 AN: 251324 AF XY: 0.746

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 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

African (AFR) AF: 0.475 AC: 15885 AN: 33462

American (AMR) AF: 0.812 AC: 36324 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 19477 AN: 26134

East Asian (EAS) AF: 0.734 AC: 29120 AN: 39700

South Asian (SAS) AF: 0.682 AC: 58808 AN: 86252

European-Finnish (FIN) AF: 0.775 AC: 41372 AN: 53412

Middle Eastern (MID) AF: 0.713 AC: 4109 AN: 5764

European-Non Finnish (NFE) AF: 0.774 AC: 859710 AN: 1111396

Other (OTH) AF: 0.746 AC: 45056 AN: 60374

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

African (AFR) AF: 0.491 AC: 20336 AN: 41410

American (AMR) AF: 0.772 AC: 11799 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2543 AN: 3466

East Asian (EAS) AF: 0.746 AC: 3840 AN: 5150

South Asian (SAS) AF: 0.679 AC: 3269 AN: 4816

European-Finnish (FIN) AF: 0.782 AC: 8281 AN: 10592

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.768 AC: 52209 AN: 67974

Other (OTH) AF: 0.708 AC: 1490 AN: 2106

Alfa AF: 0.744 Hom.: 154115

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;.
PhyloP100		0.18
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
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

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