Variant chr1-103534778-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000423855.7(RNPC3):c.364G>A(p.Asp122Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000263 in 1,523,302 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

RNPC3
ENST00000423855.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.30

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]

RNPC3 links:

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=0.1513477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNPC3	NM_017619.4 linkuse as main transcript	c.364G>A	p.Asp122Asn	missense_variant	4/15	ENST00000423855.7	NP_060089.1	Q96LT9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNPC3	ENST00000423855.7 linkuse as main transcript	c.364G>A	p.Asp122Asn	missense_variant	4/15	1	NM_017619.4	ENSP00000391432.1		Q96LT9-1

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151310

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

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

GnomAD3 exomes

AF:

0.0000218

AC:

AN:

137522

Hom.:

AF XY:

0.0000271

AC XY:

AN XY:

73790

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000127

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000219

AC:

AN:

1371992

Hom.:

Cov.:

AF XY:

0.00000295

AC XY:

AN XY:

677680

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000866

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151310

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73848

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000658

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

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2022

The c.364G>A (p.D122N) alteration is located in exon 1 (coding exon 1) of the RNPC3 gene. This alteration results from a G to A substitution at nucleotide position 364, causing the aspartic acid (D) at amino acid position 122 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

.;T;T;T

Eigen

Benign

-0.049

Eigen_PC

Benign

0.098

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

T;T;.;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.5

N;N;N;N

REVEL

Benign

0.066

Sift

Benign

0.036

D;D;D;D

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.023

.;.;B;B

Vest4

0.21

MutPred

0.26

Loss of solvent accessibility (P = 0.0387);Loss of solvent accessibility (P = 0.0387);Loss of solvent accessibility (P = 0.0387);Loss of solvent accessibility (P = 0.0387);

MVP

0.45

MPC

0.081

ClinPred

0.32

GERP RS

5.7

Varity_R

0.097

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over