16-2254337-G-A

Variant names:

• chr16-2254337-G-A
• rs9796949
• NM_080594.4:c.819-274C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

ENSG00000299317 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RNPS1	NM_080594.4	c.819-274C>T		intron_variant	Intron 7 of 7	ENST00000320225.10	NP_542161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNPS1	ENST00000320225.10	c.819-274C>T		intron_variant	Intron 7 of 7	1	NM_080594.4	ENSP00000315859.5
RNPS1	ENST00000301730.12	c.819-274C>T		intron_variant	Intron 8 of 8	2		ENSP00000301730.8

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

African (AFR) AF: 0.0752 AC: 3098 AN: 41182

American (AMR) AF: 0.448 AC: 6815 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1192 AN: 3462

East Asian (EAS) AF: 0.462 AC: 2365 AN: 5120

South Asian (SAS) AF: 0.409 AC: 1958 AN: 4790

European-Finnish (FIN) AF: 0.406 AC: 4240 AN: 10456

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26500 AN: 67834

Other (OTH) AF: 0.343 AC: 720 AN: 2100

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
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

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: rs9796949; hg19: chr16-2304338;