rs9796949

chr16-2254337-G-Achr16-2254337-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080594.4(RNPS1):c.819-274C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,370 control chromosomes in the GnomAD database, including 9,035 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (9035 hom., cov: 30)
• Consequence: RNPS1 NM_080594.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNPS1	NM_080594.4	c.819-274C>T		intron_variant		ENST00000320225.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNPS1	ENST00000320225.10	c.819-274C>T		intron_variant		1	NM_080594.4	A1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47172 AN: 151258 Hom.: 9026 Cov.: 30

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.343

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.312 AC: 47203 AN: 151370 Hom.: 9035 Cov.: 30 AF XY: 0.317 AC XY: 23451 AN XY: 73940

Gnomad4 AFR AF: 0.0752

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.343

Alfa AF: 0.335 Hom.: 1602

Bravo AF: 0.307

Asia WGS AF: 0.396 AC: 1376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.5
Dann	Benign	0.57

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

Other links and lift over

dbSNP: rs9796949; hg19: chr16-2304338;