NM_018226.6:c.293C>T

Variant names:

• chr2-240568879-C-T
• NM_018226.6:c.293C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018226.6(RNPEPL1):​c.293C>T​(p.Ala98Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RNPEPL1 NM_018226.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.71
• Publications: 0 publications found

Genes affected

RNPEPL1 (HGNC:10079): (arginyl aminopeptidase like 1) Enables metalloaminopeptidase activity. Involved in proteolysis. [provided by Alliance of Genome Resources, Apr 2022]

ANKMY1 (HGNC:20987): (ankyrin repeat and MYND domain containing 1) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17581508).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018226.6. 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
	RNPEPL1	NM_018226.6	MANE Select	c.293C>T	p.Ala98Val	missense	Exon 1 of 11	NP_060696.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNPEPL1	ENST00000270357.10	TSL:1 MANE Select	c.293C>T	p.Ala98Val	missense	Exon 1 of 11	ENSP00000270357.4	Q9HAU8
	RNPEPL1	ENST00000971323.1		c.293C>T	p.Ala98Val	missense	Exon 1 of 11	ENSP00000641382.1
	RNPEPL1	ENST00000971322.1		c.293C>T	p.Ala98Val	missense	Exon 1 of 11	ENSP00000641381.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1090950 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 528628

African (AFR) AF: 0.00 AC: 0 AN: 21420

American (AMR) AF: 0.00 AC: 0 AN: 12010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14324

East Asian (EAS) AF: 0.00 AC: 0 AN: 20818

South Asian (SAS) AF: 0.00 AC: 0 AN: 36048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2810

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 920644

Other (OTH) AF: 0.00 AC: 0 AN: 41844

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Benign	0.97
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.18	T
PhyloP100		-1.7
PrimateAI	Pathogenic	0.87	D
GERP RS		0.56
PromoterAI		-0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.027
gMVP		0.25
Mutation Taster		=300/0	polymorphism

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

hg19: chr2-241508296;