2-240568921-G-T

Variant names:

• chr2-240568921-G-T
• rs1055979792
• NM_018226.6:c.335G>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.335G>T​(p.Gly112Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000612 in 1,307,280 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. G112R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000052 (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: 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=0.2402671).

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>T	p.Gly112Val	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>T	p.Gly112Val	missense	Exon 1 of 11	ENSP00000270357.4	Q9HAU8
	RNPEPL1	ENST00000971323.1		c.335G>T	p.Gly112Val	missense	Exon 1 of 11	ENSP00000641382.1
	RNPEPL1	ENST00000971322.1		c.335G>T	p.Gly112Val	missense	Exon 1 of 11	ENSP00000641381.1

Frequencies

GnomAD3 genomes AF: 0.0000136 AC: 2 AN: 146696 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: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000303

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: 0.00000517 AC: 6 AN: 1160584 Hom.: 0 Cov.: 32 AF XY: 0.00000531 AC XY: 3 AN XY: 565358

African (AFR) AF: 0.00 AC: 0 AN: 23390

American (AMR) AF: 0.00 AC: 0 AN: 10320

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 26140

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: 0.00000620 AC: 6 AN: 967812

Other (OTH) AF: 0.00 AC: 0 AN: 46482

GnomAD4 genome AF: 0.0000136 AC: 2 AN: 146696 Hom.: 0 Cov.: 32 AF XY: 0.0000140 AC XY: 1 AN XY: 71642

African (AFR) AF: 0.00 AC: 0 AN: 39876

American (AMR) AF: 0.00 AC: 0 AN: 14880

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4856

South Asian (SAS) AF: 0.00 AC: 0 AN: 4652

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 248

European-Non Finnish (NFE) AF: 0.0000303 AC: 2 AN: 66112

Other (OTH) AF: 0.00 AC: 0 AN: 2018

Alfa AF: 0.00 Hom.: 0

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	0.10
BayesDel_noAF	Benign	-0.71
CADD	Benign	20
DANN	Benign	0.94
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.24	T
PhyloP100		1.0
PrimateAI	Pathogenic	0.86	D
GERP RS		2.2
PromoterAI		-0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.076
gMVP		0.52
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;