1-201989008-G-C

Variant names:

• chr1-201989008-G-C
• rs79043888
• NM_020216.4:c.552G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_020216.4(RNPEP):​c.552G>C​(p.Thr184Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T184T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNPEP NM_020216.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-1.66 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020216.4. 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
	RNPEP	NM_020216.4	MANE Select	c.552G>C	p.Thr184Thr	synonymous	Exon 2 of 11	NP_064601.3
	RNPEP	NM_001319182.2		c.159G>C	p.Thr53Thr	synonymous	Exon 2 of 11	NP_001306111.1
	RNPEP	NM_001319183.2		c.-316G>C		5_prime_UTR	Exon 2 of 10	NP_001306112.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNPEP	ENST00000295640.9	TSL:1 MANE Select	c.552G>C	p.Thr184Thr	synonymous	Exon 2 of 11	ENSP00000295640.4	Q9H4A4
	RNPEP	ENST00000471105.5	TSL:1	n.264G>C		non_coding_transcript_exon	Exon 2 of 10
	RNPEP	ENST00000967255.1		c.552G>C	p.Thr184Thr	synonymous	Exon 2 of 11	ENSP00000637314.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-1.7
Mutation Taster		=99/1	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: rs79043888; hg19: chr1-201958136;