chr1-201997416-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

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, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNPEP	NM_020216.4	c.952T>C	p.Ser318Pro	missense_variant	Exon 5 of 11	ENST00000295640.9	NP_064601.3
RNPEP	NM_001319182.2	c.559T>C	p.Ser187Pro	missense_variant	Exon 5 of 11		NP_001306111.1
RNPEP	NM_001319183.2	c.82T>C	p.Ser28Pro	missense_variant	Exon 4 of 10		NP_001306112.1
RNPEP	NM_001319184.2	c.82T>C	p.Ser28Pro	missense_variant	Exon 4 of 10		NP_001306113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNPEP	ENST00000295640.9	c.952T>C	p.Ser318Pro	missense_variant	Exon 5 of 11	1	NM_020216.4	ENSP00000295640.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.80	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.5	H;.;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.9	D;D;D;D
REVEL	Benign	0.29
Sift	Benign	0.070	T;T;D;D
Sift4G	Benign	0.087	T;T;D;D
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

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: chr1-201966544;