15-69268521-C-T

Variant names:

• chr15-69268521-C-T
• rs140697904
• NM_015554.3:c.1131C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015554.3(GLCE):​c.1131C>T​(p.Pro377Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P377P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GLCE NM_015554.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=0.261 with no splicing effect.

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.1131C>T	p.Pro377Pro	synonymous	Exon 5 of 5	NP_056369.1	O94923
	GLCE	NM_001324093.2		c.1131C>T	p.Pro377Pro	synonymous	Exon 6 of 6	NP_001311022.1	O94923
	GLCE	NM_001324094.2		c.1131C>T	p.Pro377Pro	synonymous	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.1131C>T	p.Pro377Pro	synonymous	Exon 5 of 5	ENSP00000261858.2	O94923
	GLCE	ENST00000559420.2	TSL:1	c.939C>T	p.Pro313Pro	synonymous	Exon 3 of 3	ENSP00000454092.1	H0YNP1
	GLCE	ENST00000897735.1		c.834C>T	p.Pro278Pro	synonymous	Exon 5 of 5	ENSP00000567794.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461832 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727218

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.61
PhyloP100		0.26

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: rs140697904; hg19: chr15-69560860;