10-103247771-C-T

Variant names:

• chr10-103247771-C-T
• rs4917386
• NM_001143909.1:c.*1088C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

NT5C2 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 45

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Orphanet

ENSG00000306663 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143909.1. 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
	RPEL1	NM_001143909.1	MANE Select	c.*1088C>T		3_prime_UTR	Exon 1 of 1	NP_001137381.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPEL1	ENST00000441178.2	TSL:6 MANE Select	c.*1088C>T		3_prime_UTR	Exon 1 of 1	ENSP00000476672.1
	NT5C2	ENST00000674696.1		c.-25+28445G>A		intron	N/A	ENSP00000502679.1
	NT5C2	ENST00000675326.1		c.-169+29383G>A		intron	N/A	ENSP00000502205.1

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

African (AFR) AF: 0.500 AC: 2 AN: 4

American (AMR) AF: 0.500 AC: 2 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.313 AC: 4589 AN: 14682

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.333 AC: 28 AN: 84

Other (OTH) AF: 0.311 AC: 28 AN: 90

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

African (AFR) AF: 0.359 AC: 14825 AN: 41284

American (AMR) AF: 0.406 AC: 6175 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1232 AN: 3468

East Asian (EAS) AF: 0.403 AC: 2075 AN: 5150

South Asian (SAS) AF: 0.307 AC: 1472 AN: 4800

European-Finnish (FIN) AF: 0.314 AC: 3256 AN: 10372

Middle Eastern (MID) AF: 0.321 AC: 93 AN: 290

European-Non Finnish (NFE) AF: 0.354 AC: 24015 AN: 67892

Other (OTH) AF: 0.368 AC: 776 AN: 2106

Alfa AF: 0.337 Hom.: 5400

Bravo AF: 0.371

Asia WGS AF: 0.364 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.25
DANN	Benign	0.59
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs4917386; hg19: chr10-105007528;