2-240568795-C-G

Variant names:

• chr2-240568795-C-G
• rs1178529523
• NM_018226.6:c.209C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018226.6(RNPEPL1):​c.209C>G​(p.Pro70Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000107 in 935,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P70H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: RNPEPL1 NM_018226.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30288294).

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.209C>G	p.Pro70Arg	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.209C>G	p.Pro70Arg	missense	Exon 1 of 11	ENSP00000270357.4	Q9HAU8
	RNPEPL1	ENST00000971323.1		c.209C>G	p.Pro70Arg	missense	Exon 1 of 11	ENSP00000641382.1
	RNPEPL1	ENST00000971322.1		c.209C>G	p.Pro70Arg	missense	Exon 1 of 11	ENSP00000641381.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000107 AC: 1 AN: 935042 Hom.: 0 Cov.: 31 AF XY: 0.00000225 AC XY: 1 AN XY: 444026

African (AFR) AF: 0.00 AC: 0 AN: 17588

American (AMR) AF: 0.00 AC: 0 AN: 4244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7916

East Asian (EAS) AF: 0.00 AC: 0 AN: 9852

South Asian (SAS) AF: 0.00 AC: 0 AN: 26070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2086

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 825292

Other (OTH) AF: 0.00 AC: 0 AN: 32500

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Benign	0.93
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.30	T
PhyloP100		1.3
PrimateAI	Pathogenic	0.86	D
GERP RS		1.9
PromoterAI		0.068	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.058
gMVP		0.23
Mutation Taster		=296/4	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

dbSNP: rs1178529523; hg19: chr2-241508212;