chr1-201982737-A-T

Position:

• chr1-201982737-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020216.4(RNPEP):​c.71A>T​(p.Asp24Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNPEP NM_020216.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.46

Genes affected

RNPEP (HGNC:10078): (arginyl aminopeptidase) Predicted to enable metalloaminopeptidase activity. Predicted to be involved in proteolysis. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.827

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNPEP	NM_020216.4	c.71A>T	p.Asp24Val	missense_variant	1/11	ENST00000295640.9	NP_064601.3
RNPEP	NM_001319183.2	c.-797A>T		5_prime_UTR_variant	1/10		NP_001306112.1
RNPEP	NM_001319184.2	c.-651A>T		5_prime_UTR_variant	1/10		NP_001306113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNPEP	ENST00000295640.9	c.71A>T	p.Asp24Val	missense_variant	1/11	1	NM_020216.4	ENSP00000295640	P1
RNPEP	ENST00000367286.7	c.71A>T	p.Asp24Val	missense_variant	1/10	5		ENSP00000356255
RNPEP	ENST00000481780.5	n.66+300A>T		intron_variant, non_coding_transcript_variant		5
RNPEP	ENST00000487116.5			upstream_gene_variant		3		ENSP00000478325

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2023

The c.71A>T (p.D24V) alteration is located in exon 1 (coding exon 1) of the RNPEP gene. This alteration results from a A to T substitution at nucleotide position 71, causing the aspartic acid (D) at amino acid position 24 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.66	D;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	D;T
M_CAP	Pathogenic	0.63	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.90	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-5.4	D;D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;.
Vest4		0.63
MutPred		0.50		Gain of sheet (P = 0.0073);Gain of sheet (P = 0.0073);
MVP		0.51
MPC		0.80
ClinPred		1.0	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.86
gMVP		0.71

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-201951865;