1-103533842-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017619.4(RNPC3):​c.344C>T​(p.Ser115Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000758 in 1,319,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 31)
Exomes 𝑓: 7.6e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RNPC3
NM_017619.4 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32
Variant links:
Genes affected
RNPC3 (HGNC:18666): (RNA binding region (RNP1, RRM) containing 3) Two types of spliceosomes catalyze splicing of pre-mRNAs. The major U2-type spliceosome is found in all eukaryotes and removes U2-type introns, which represent more than 99% of pre-mRNA introns. The minor U12-type spliceosome is found in some eukaryotes and removes U12-type introns, which are rare and have distinct splice consensus signals. The U12-type spliceosome consists of several small nuclear RNAs and associated proteins. This gene encodes a 65K protein that is a component of the U12-type spliceosome. This protein contains two RNA recognition motifs (RRMs), suggesting that it may contact one of the small nuclear RNAs of the minor spliceosome. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13698408).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RNPC3NM_017619.4 linkc.344C>T p.Ser115Phe missense_variant Exon 3 of 15 ENST00000423855.7 NP_060089.1 Q96LT9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RNPC3ENST00000423855.7 linkc.344C>T p.Ser115Phe missense_variant Exon 3 of 15 1 NM_017619.4 ENSP00000391432.1 Q96LT9-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
144052
Hom.:
0
Cov.:
31
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
7.58e-7
AC:
1
AN:
1319662
Hom.:
0
Cov.:
24
AF XY:
0.00000153
AC XY:
1
AN XY:
654210
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000287
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
144052
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
69650
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Isolated growth hormone deficiency, type 5 Uncertain:1
May 13, 2020
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.071
.;T;T;T
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.51
FATHMM_MKL
Benign
0.41
N
LIST_S2
Benign
0.51
T;T;.;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.14
T;T;T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.9
N;D;N;N
REVEL
Benign
0.039
Sift
Uncertain
0.020
D;D;D;D
Sift4G
Uncertain
0.011
D;D;D;D
Polyphen
0.48
.;.;P;P
Vest4
0.14
MutPred
0.24
Loss of phosphorylation at S115 (P = 0.0063);Loss of phosphorylation at S115 (P = 0.0063);Loss of phosphorylation at S115 (P = 0.0063);Loss of phosphorylation at S115 (P = 0.0063);
MVP
0.10
MPC
0.086
ClinPred
0.48
T
GERP RS
2.5
Varity_R
0.045
gMVP
0.25

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: chr1-104076464; API