2-240568921-G-A

Variant names:

• chr2-240568921-G-A
• rs1055979792
• NM_018226.6:c.335G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018226.6(RNPEPL1):​c.335G>A​(p.Gly112Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,307,412 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. 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. G112V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: RNPEPL1 NM_018226.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18342021).

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.335G>A	p.Gly112Glu	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.335G>A	p.Gly112Glu	missense	Exon 1 of 11	ENSP00000270357.4	Q9HAU8
	RNPEPL1	ENST00000971323.1		c.335G>A	p.Gly112Glu	missense	Exon 1 of 11	ENSP00000641382.1
	RNPEPL1	ENST00000971322.1		c.335G>A	p.Gly112Glu	missense	Exon 1 of 11	ENSP00000641381.1

Frequencies

GnomAD3 genomes AF: 0.000348 AC: 51 AN: 146696 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000672

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD2 exomes AF: 0.00 AC: 0 AN: 17132 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000258 AC: 30 AN: 1160586 Hom.: 0 Cov.: 32 AF XY: 0.0000230 AC XY: 13 AN XY: 565358

African (AFR) AF: 0.000983 AC: 23 AN: 23390

American (AMR) AF: 0.000388 AC: 4 AN: 10320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15638

East Asian (EAS) AF: 0.00 AC: 0 AN: 26142

South Asian (SAS) AF: 0.00 AC: 0 AN: 41948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3168

European-Non Finnish (NFE) AF: 0.00000103 AC: 1 AN: 967812

Other (OTH) AF: 0.0000430 AC: 2 AN: 46482

GnomAD4 genome AF: 0.000347 AC: 51 AN: 146826 Hom.: 0 Cov.: 32 AF XY: 0.000334 AC XY: 24 AN XY: 71768

African (AFR) AF: 0.00103 AC: 41 AN: 39996

American (AMR) AF: 0.000671 AC: 10 AN: 14900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3412

East Asian (EAS) AF: 0.00 AC: 0 AN: 4840

South Asian (SAS) AF: 0.00 AC: 0 AN: 4646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 242

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66104

Other (OTH) AF: 0.00 AC: 0 AN: 2044

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000363

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	-0.69
CADD	Benign	17
DANN	Benign	0.97
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.18	T
PhyloP100		1.0
PrimateAI	Pathogenic	0.88	D
GERP RS		2.2
PromoterAI		-0.048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.092
gMVP		0.46
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

dbSNP: rs1055979792; hg19: chr2-241508338;