Variant 16-2263220-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_080594.4(RNPS1):c.295T>C(p.Ser99Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RNPS1
NM_080594.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.25

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38542035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNPS1	NM_080594.4 linkuse as main transcript	c.295T>C	p.Ser99Pro	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.295T>C	p.Ser99Pro	missense_variant	4/8	1	NM_080594.4	ENSP00000315859.5		Q15287-1
RNPS1	ENST00000301730.12 linkuse as main transcript	c.295T>C	p.Ser99Pro	missense_variant	5/9	2		ENSP00000301730.8		Q15287-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246300

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133688

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000913

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461396

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726980

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:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 28, 2021

The c.295T>C (p.S99P) alteration is located in exon 4 (coding exon 3) of the RNPS1 gene. This alteration results from a T to C substitution at nucleotide position 295, causing the serine (S) at amino acid position 99 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

Uncertain

0.50

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

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

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

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

M_CAP

Benign

0.0097

MetaRNN

Benign

0.39

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

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.8

L;L;.;L;L;L;.;.;.;.;.;.;.

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.9

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

REVEL

Benign

0.22

Sift

Uncertain

0.0080

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

Sift4G

Uncertain

0.0080

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

Polyphen

0.97

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

Vest4

0.47

MutPred

0.29

Loss of phosphorylation at S99 (P = 0);Loss of phosphorylation at S99 (P = 0);.;Loss of phosphorylation at S99 (P = 0);Loss of phosphorylation at S99 (P = 0);Loss of phosphorylation at S99 (P = 0);.;Loss of phosphorylation at S99 (P = 0);Loss of phosphorylation at S99 (P = 0);Loss of phosphorylation at S99 (P = 0);Loss of phosphorylation at S99 (P = 0);Loss of phosphorylation at S99 (P = 0);Loss of phosphorylation at S99 (P = 0);

MVP

0.38

MPC

0.59

ClinPred

0.88

GERP RS

6.1

Varity_R

0.65

gMVP

0.31

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