Genetic Variant NM_080594.4:c.893G>C (chr16-2253989-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080594.4(RNPS1):c.893G>C(p.Arg298Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000717 in 1,394,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R298H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

RNPS1
NM_080594.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.04

Publications

0 publications found

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:

ENSG00000299317 (HGNC:):

ENSG00000299317 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1938819).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNPS1	NM_080594.4 link	c.893G>C	p.Arg298Pro	missense_variant	Exon 8 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.893G>C	p.Arg298Pro	missense_variant	Exon 8 of 8	1	NM_080594.4	ENSP00000315859.5		Q15287-1
RNPS1	ENST00000301730.12 link	c.893G>C	p.Arg298Pro	missense_variant	Exon 9 of 9	2		ENSP00000301730.8		Q15287-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000631

AC:

AN:

158456

AF XY:

0.0000119

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000861

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.17e-7

AC:

AN:

1394970

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

687518

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31346

American (AMR)

AF:

0.00

AC:

AN:

35080

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24596

East Asian (EAS)

AF:

0.0000278

AC:

AN:

35928

South Asian (SAS)

AF:

0.00

AC:

AN:

78734

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5622

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076462

Other (OTH)

AF:

0.00

AC:

AN:

57730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000895

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.011

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.48

M_CAP

Uncertain

0.085

MetaRNN

Benign

0.19

PhyloP100

7.0

PROVEAN

Benign

0.29

Sift

Uncertain

0.0050

Vest4

0.35

MVP

0.52

ClinPred

0.49

GERP RS

5.2

Varity_R

0.61

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over