chr15-69268328-C-T

Variant names:

• chr15-69268328-C-T
• rs957160493
• NM_015554.3:c.938C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015554.3(GLCE):​c.938C>T​(p.Thr313Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLCE NM_015554.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.79
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLCE	NM_015554.3	MANE Select	c.938C>T	p.Thr313Ile	missense	Exon 5 of 5	NP_056369.1	O94923
	GLCE	NM_001324093.2		c.938C>T	p.Thr313Ile	missense	Exon 6 of 6	NP_001311022.1	O94923
	GLCE	NM_001324094.2		c.938C>T	p.Thr313Ile	missense	Exon 6 of 6	NP_001311023.1	O94923

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLCE	ENST00000261858.7	TSL:1 MANE Select	c.938C>T	p.Thr313Ile	missense	Exon 5 of 5	ENSP00000261858.2	O94923
	GLCE	ENST00000559420.2	TSL:1	c.746C>T	p.Thr249Ile	missense	Exon 3 of 3	ENSP00000454092.1	H0YNP1
	GLCE	ENST00000897735.1		c.641C>T	p.Thr214Ile	missense	Exon 5 of 5	ENSP00000567794.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	2.0	M
PhyloP100		7.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.21
Sift	Benign	0.20	T
Sift4G	Benign	0.22	T
Polyphen		0.99	D
Vest4		0.63
MutPred		0.30		Loss of sheet (P = 0.0104)
MVP		0.70
MPC		1.1
ClinPred		0.84	D
GERP RS		5.6
Varity_R		0.24
gMVP		0.41

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: rs957160493; hg19: chr15-69560667;