chr2-240568906-C-G

Variant names:

• chr2-240568906-C-G
• rs946218997
• NM_018226.6:c.320C>G

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.320C>G​(p.Ser107Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000313 in 1,278,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S107F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: RNPEPL1 NM_018226.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.701
• 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=0.23246324).

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.320C>G	p.Ser107Cys	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.320C>G	p.Ser107Cys	missense	Exon 1 of 11	ENSP00000270357.4	Q9HAU8
	RNPEPL1	ENST00000971323.1		c.320C>G	p.Ser107Cys	missense	Exon 1 of 11	ENSP00000641382.1
	RNPEPL1	ENST00000971322.1		c.320C>G	p.Ser107Cys	missense	Exon 1 of 11	ENSP00000641381.1

Frequencies

GnomAD3 genomes AF: 0.00000668 AC: 1 AN: 149598 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000266 AC: 3 AN: 1128740 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 547352

African (AFR) AF: 0.00 AC: 0 AN: 22578

American (AMR) AF: 0.00 AC: 0 AN: 8790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14264

East Asian (EAS) AF: 0.000119 AC: 3 AN: 25146

South Asian (SAS) AF: 0.00 AC: 0 AN: 35916

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2976

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 950518

Other (OTH) AF: 0.00 AC: 0 AN: 44706

GnomAD4 genome AF: 0.00000668 AC: 1 AN: 149710 Hom.: 0 Cov.: 32 AF XY: 0.0000137 AC XY: 1 AN XY: 73108

African (AFR) AF: 0.00 AC: 0 AN: 41012

American (AMR) AF: 0.00 AC: 0 AN: 15066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5066

South Asian (SAS) AF: 0.00 AC: 0 AN: 4772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9860

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67228

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.096
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Benign	0.86
DEOGEN2	Benign	0.19	T
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.23	T
PhyloP100		-0.70
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.2	N
Sift	Benign	0.033	D
GERP RS		2.2
PromoterAI		-0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.12
gMVP		0.39
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: rs946218997; hg19: chr2-241508323;