rs2093608722

Variant names:

• chr16-2262840-G-C
• rs2093608722
• NM_080594.4:c.422C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_080594.4(RNPS1):​c.422C>G​(p.Ser141Cys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNPS1 NM_080594.4 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.46
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080594.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNPS1	NM_080594.4	MANE Select	c.422C>G	p.Ser141Cys	missense splice_region	Exon 5 of 8	NP_542161.1	Q15287-1
	RNPS1	NM_001286625.1		c.422C>G	p.Ser141Cys	missense splice_region	Exon 5 of 8	NP_001273554.1	D3DU92
	RNPS1	NM_006711.5		c.422C>G	p.Ser141Cys	missense splice_region	Exon 5 of 8	NP_006702.1	Q15287-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNPS1	ENST00000320225.10	TSL:1 MANE Select	c.422C>G	p.Ser141Cys	missense splice_region	Exon 5 of 8	ENSP00000315859.5	Q15287-1
	RNPS1	ENST00000301730.12	TSL:2	c.422C>G	p.Ser141Cys	missense splice_region	Exon 6 of 9	ENSP00000301730.8	Q15287-1
	RNPS1	ENST00000397086.6	TSL:1	c.422C>G	p.Ser141Cys	missense splice_region	Exon 5 of 8	ENSP00000380275.2	Q15287-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.36	T
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.90
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		9.5
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.30
Sift	Benign	0.062	T
Sift4G	Uncertain	0.018	D
Polyphen		0.99	D
Vest4		0.52
MutPred		0.30		Loss of phosphorylation at S141 (P = 2e-04)
MVP		0.47
MPC		0.45
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.60
gMVP		0.66

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

Other links and lift over

dbSNP: rs2093608722; hg19: chr16-2312841;