10-103247771-C-T

Position:

• chr10-103247771-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143909.1(RPEL1):​c.*1088C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 166,336 control chromosomes in the GnomAD database, including 10,563 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (9827 hom., cov: 30)
  • Exomes 𝑓: 0.31 (736 hom.)
• Consequence: RPEL1 NM_001143909.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

Genes affected

RPEL1 (HGNC:45241): (ribulose-5-phosphate-3-epimerase like 1) Predicted to enable metal ion binding activity and ribulose-phosphate 3-epimerase activity. Predicted to be involved in cellular carbohydrate metabolic process; pentose catabolic process; and pentose-phosphate shunt, non-oxidative branch. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

NT5C2 (HGNC:8022): (5'-nucleotidase, cytosolic II) This gene encodes a hydrolase that serves as an important role in cellular purine metabolism by acting primarily on inosine 5'-monophosphate and other purine nucleotides. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPEL1	NM_001143909.1	c.*1088C>T		3_prime_UTR_variant	1/1	ENST00000441178.2	NP_001137381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPEL1	ENST00000441178.2	c.*1088C>T		3_prime_UTR_variant	1/1		NM_001143909.1	ENSP00000476672	P1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54191 AN: 151352 Hom.: 9810 Cov.: 30

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.369

GnomAD4 exome AF: 0.313 AC: 4650 AN: 14870 Hom.: 736 Cov.: 0 AF XY: 0.317 AC XY: 2232 AN XY: 7050

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.311

GnomAD4 genome AF: 0.358 AC: 54245 AN: 151466 Hom.: 9827 Cov.: 30 AF XY: 0.357 AC XY: 26399 AN XY: 73894

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.368

Alfa AF: 0.335 Hom.: 4878

Bravo AF: 0.371

Asia WGS AF: 0.364 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.25
DANN	Benign	0.59

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: rs4917386; hg19: chr10-105007528;