10-103246417-A-G

Position:

• chr10-103246417-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001143909.1(RPEL1):​c.421A>G​(p.Met141Val) variant causes a missense change. 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: RPEL1 NM_001143909.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.91

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 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/exons	MANE	Protein	UniProt
RPEL1	NM_001143909.1	c.421A>G	p.Met141Val	missense_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.421A>G	p.Met141Val	missense_variant	1/1		NM_001143909.1	ENSP00000476672	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 10, 2024

The c.421A>G (p.M141V) alteration is located in exon 1 (coding exon 1) of the RPEL1 gene. This alteration results from a A to G substitution at nucleotide position 421, causing the methionine (M) at amino acid position 141 to be replaced by a valine (V). 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	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	19
DANN	Benign	0.79
DEOGEN2	Uncertain	0.50	D
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0032	T
MetaRNN	Uncertain	0.43	T
MutationAssessor	Pathogenic	4.6	H
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.45
MVP		0.030
MPC		0.49
GERP RS		0.91
Varity_R		0.17
gMVP		0.96

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-105006174;