dbSNP rs59656945: RNPS1:p.Val208Leu (chr16-2262332-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_080594.4(RNPS1):c.622G>T(p.Val208Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,736 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RNPS1
NM_080594.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.43

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNPS1	NM_080594.4 link	c.622G>T	p.Val208Leu	missense_variant	Exon 6 of 8	ENST00000320225.10	NP_542161.1	Q15287-1D3DU92

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNPS1	ENST00000320225.10 link	c.622G>T	p.Val208Leu	missense_variant	Exon 6 of 8	1	NM_080594.4	ENSP00000315859.5		Q15287-1
RNPS1	ENST00000301730.12 link	c.622G>T	p.Val208Leu	missense_variant	Exon 7 of 9	2		ENSP00000301730.8		Q15287-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461736

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727148

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

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

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.79

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

M_CAP

Benign

0.071

MetaRNN

Uncertain

0.66

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

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.7

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

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.7

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

REVEL

Uncertain

0.29

Sift

Uncertain

0.010

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

Sift4G

Uncertain

0.013

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

Polyphen

0.99

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

Vest4

0.62

MutPred

0.60

Gain of ubiquitination at K203 (P = 0.1295);Gain of ubiquitination at K203 (P = 0.1295);.;.;Gain of ubiquitination at K203 (P = 0.1295);.;Gain of ubiquitination at K203 (P = 0.1295);.;Gain of ubiquitination at K203 (P = 0.1295);.;Gain of ubiquitination at K203 (P = 0.1295);Gain of ubiquitination at K203 (P = 0.1295);

MVP

0.89

MPC

1.3

ClinPred

0.96

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.74

gMVP

0.90

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over