chr15-69269179-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015554.3(GLCE):​c.1789G>C​(p.Val597Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 31)
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043646008).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015554.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLCE	NM_015554.3	MANE Select	c.1789G>C	p.Val597Leu	missense	Exon 5 of 5	NP_056369.1
	GLCE	NM_001324093.2		c.1789G>C	p.Val597Leu	missense	Exon 6 of 6	NP_001311022.1
	GLCE	NM_001324094.2		c.1789G>C	p.Val597Leu	missense	Exon 6 of 6	NP_001311023.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLCE	ENST00000261858.7	TSL:1 MANE Select	c.1789G>C	p.Val597Leu	missense	Exon 5 of 5	ENSP00000261858.2
	GLCE	ENST00000559420.2	TSL:1	c.1597G>C	p.Val533Leu	missense	Exon 3 of 3	ENSP00000454092.1
	PAQR5-DT	ENST00000746778.1		n.446-3746C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.14
DANN	Benign	0.27
DEOGEN2	Benign	0.24	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.18
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.057
Sift	Benign	0.51	T
Sift4G	Benign	0.72	T
Polyphen		0.0	B
Vest4		0.069
MutPred		0.54		Gain of catalytic residue at V597 (P = 0.002)
MVP		0.29
MPC		0.38
ClinPred		0.052	T
GERP RS		-3.2
Varity_R		0.14
gMVP		0.33

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;