15-69268328-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLCE	NM_015554.3	c.938C>T	p.Thr313Ile	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.938C>T	p.Thr313Ile	missense_variant	Exon 5 of 5	1	NM_015554.3	ENSP00000261858.2
GLCE	ENST00000559420.2	c.746C>T	p.Thr249Ile	missense_variant	Exon 3 of 3	1		ENSP00000454092.1
GLCE	ENST00000559500.1	n.743C>T		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.938C>T (p.T313I) alteration is located in exon 5 (coding exon 3) of the GLCE gene. This alteration results from a C to T substitution at nucleotide position 938, causing the threonine (T) at amino acid position 313 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.21
Sift	Benign	0.20	T;T
Sift4G	Benign	0.22	T;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

Publications

LitVar

Other links and lift over

dbSNP: rs957160493; hg19: chr15-69560667;