Variant 16-2263132-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000320225.10(RNPS1):c.383G>C(p.Arg128Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,613,178 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

RNPS1
ENST00000320225.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.11

Variant links:

Genes affected

RNPS1 (HGNC:10080): (RNA binding protein with serine rich domain 1) This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein binds to the mRNA and remains bound after nuclear export, acting as a nucleocytoplasmic shuttling protein. This protein contains many serine residues. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

RNPS1 links:

RNPS1 (HGNC:):

RNPS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNPS1	NM_080594.4 linkuse as main transcript	c.383G>C	p.Arg128Pro	missense_variant	4/8	ENST00000320225.10	NP_542161.1	Q15287-1D3DU92

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNPS1	ENST00000320225.10 linkuse as main transcript	c.383G>C	p.Arg128Pro	missense_variant	4/8	1	NM_080594.4	ENSP00000315859.5		Q15287-1
RNPS1	ENST00000301730.12 linkuse as main transcript	c.383G>C	p.Arg128Pro	missense_variant	5/9	2		ENSP00000301730.8		Q15287-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248028

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134514

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000996

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:

0.00000890

AC:

AN:

1461086

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726828

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2023

The c.383G>C (p.R128P) alteration is located in exon 4 (coding exon 3) of the RNPS1 gene. This alteration results from a G to C substitution at nucleotide position 383, causing the arginine (R) at amino acid position 128 to be replaced by a proline (P). 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

Pathogenic

0.89

BayesDel_addAF

Uncertain

0.091

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.084

T;T;.;T;T;.;T;T;T;T;T;T;.

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

.;.;D;.;.;T;D;D;D;D;D;D;D

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.43

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.4

M;M;.;M;M;.;M;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-2.7

D;D;N;D;D;N;D;N;D;D;D;D;D

REVEL

Benign

0.26

Sift

Benign

0.086

T;T;T;T;T;D;T;T;T;T;T;D;D

Sift4G

Benign

0.11

T;T;.;T;T;T;T;.;.;.;.;T;.

Polyphen

0.99

D;D;D;D;D;.;D;.;.;.;.;.;.

Vest4

0.59

MutPred

0.32

Loss of methylation at R128 (P = 0.0086);Loss of methylation at R128 (P = 0.0086);.;Loss of methylation at R128 (P = 0.0086);Loss of methylation at R128 (P = 0.0086);.;Loss of methylation at R128 (P = 0.0086);.;Loss of methylation at R128 (P = 0.0086);Loss of methylation at R128 (P = 0.0086);Loss of methylation at R128 (P = 0.0086);Loss of methylation at R128 (P = 0.0086);Loss of methylation at R128 (P = 0.0086);

MVP

0.38

MPC

0.67

ClinPred

0.69

GERP RS

6.1

Varity_R

0.54

gMVP

0.62

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

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