Variant 16-2264194-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_080594.4(RNPS1):c.209G>A(p.Ser70Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,208 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: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

RNPS1
NM_080594.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.70

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 59 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNPS1	NM_080594.4 linkuse as main transcript	c.209G>A	p.Ser70Asn	missense_variant	3/8	ENST00000320225.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNPS1	ENST00000320225.10 linkuse as main transcript	c.209G>A	p.Ser70Asn	missense_variant	3/8	1	NM_080594.4	A1	Q15287-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251364

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135880

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000404

AC:

AN:

1460978

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

726784

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:

0.0000522

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74372

show subpopulations

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Aug 02, 2023

The c.209G>A (p.S70N) alteration is located in exon 3 (coding exon 2) of the RNPS1 gene. This alteration results from a G to A substitution at nucleotide position 209, causing the serine (S) at amino acid position 70 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

Uncertain

0.53

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.46

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.095

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

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.91

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

M_CAP

Benign

0.013

MetaRNN

Benign

0.24

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

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

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

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.8

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

REVEL

Benign

0.067

Sift

Uncertain

0.0020

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

Sift4G

Uncertain

0.018

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

Polyphen

0.20

B;B;B;B;B;B;.;.;.;.;.;.;.;.;.

Vest4

0.44

MutPred

0.26

Loss of phosphorylation at S70 (P = 3e-04);Loss of phosphorylation at S70 (P = 3e-04);.;Loss of phosphorylation at S70 (P = 3e-04);Loss of phosphorylation at S70 (P = 3e-04);Loss of phosphorylation at S70 (P = 3e-04);.;Loss of phosphorylation at S70 (P = 3e-04);Loss of phosphorylation at S70 (P = 3e-04);Loss of phosphorylation at S70 (P = 3e-04);Loss of phosphorylation at S70 (P = 3e-04);Loss of phosphorylation at S70 (P = 3e-04);Loss of phosphorylation at S70 (P = 3e-04);Loss of phosphorylation at S70 (P = 3e-04);Loss of phosphorylation at S70 (P = 3e-04);

MVP

0.43

MPC

0.43

ClinPred

0.49

GERP RS

5.8

Varity_R

0.37

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.44

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.44

Position offset: -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