chr1-201997416-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

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

Scores

5
6
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.47
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
RNPEPNM_020216.4 linkc.952T>C p.Ser318Pro missense_variant Exon 5 of 11 ENST00000295640.9 NP_064601.3 Q9H4A4
RNPEPNM_001319182.2 linkc.559T>C p.Ser187Pro missense_variant Exon 5 of 11 NP_001306111.1 Q9H4A4
RNPEPNM_001319183.2 linkc.82T>C p.Ser28Pro missense_variant Exon 4 of 10 NP_001306112.1 Q9H4A4
RNPEPNM_001319184.2 linkc.82T>C p.Ser28Pro missense_variant Exon 4 of 10 NP_001306113.1 Q9H4A4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RNPEPENST00000295640.9 linkc.952T>C p.Ser318Pro missense_variant Exon 5 of 11 1 NM_020216.4 ENSP00000295640.4 Q9H4A4

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; API