chr1-201997416-T-C

Variant names:

• chr1-201997416-T-C
• rs374485540
• NM_020216.4:c.952T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020216.4(RNPEP):​c.952T>C​(p.Ser318Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S318T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RNPEP NM_020216.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.47
• Publications: 0 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]

ELF3-AS1 (HGNC:40211): (ELF3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.798

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.952T>C	p.Ser318Pro	missense	Exon 5 of 11	NP_064601.3
	RNPEP	NM_001319182.2		c.559T>C	p.Ser187Pro	missense	Exon 5 of 11	NP_001306111.1
	RNPEP	NM_001319183.2		c.82T>C	p.Ser28Pro	missense	Exon 4 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.952T>C	p.Ser318Pro	missense	Exon 5 of 11	ENSP00000295640.4	Q9H4A4
	RNPEP	ENST00000471105.5	TSL:1	n.661T>C		non_coding_transcript_exon	Exon 4 of 10
	RNPEP	ENST00000967255.1		c.949T>C	p.Ser317Pro	missense	Exon 5 of 11	ENSP00000637314.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		4.5
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.29
Sift	Benign	0.070	T
Sift4G	Benign	0.087	T
Polyphen		1.0	D
Vest4		0.74
MutPred		0.74		Loss of stability (P = 0.0684)
MVP		0.76
MPC		0.75
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.75
gMVP		0.86
Mutation Taster		=66/34	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: rs374485540; hg19: chr1-201966544;