Variant chr16-2255692-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_080594.4(RNPS1):c.711C>T(p.Ala237Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,613,838 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 68 hom. )

Consequence

RNPS1
NM_080594.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.687

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:

RNPS1 (HGNC:):

RNPS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 16-2255692-G-A is Benign according to our data. Variant chr16-2255692-G-A is described in ClinVar as [Benign]. Clinvar id is 770437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.687 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00396 (603/152376) while in subpopulation EAS AF= 0.0399 (207/5188). AF 95% confidence interval is 0.0355. There are 7 homozygotes in gnomad4. There are 386 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 603 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNPS1	NM_080594.4 linkuse as main transcript	c.711C>T	p.Ala237Ala	synonymous_variant	7/8	ENST00000320225.10	NP_542161.1	Q15287-1D3DU92

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNPS1	ENST00000320225.10 linkuse as main transcript	c.711C>T	p.Ala237Ala	synonymous_variant	7/8	1	NM_080594.4	ENSP00000315859.5		Q15287-1
RNPS1	ENST00000301730.12 linkuse as main transcript	c.711C>T	p.Ala237Ala	synonymous_variant	8/9	2		ENSP00000301730.8		Q15287-1

Frequencies

GnomAD3 genomes

AF:

0.00397

AC:

604

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0400

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0174

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00799

AC:

1999

AN:

250228

Hom.:

AF XY:

0.00669

AC XY:

907

AN XY:

135636

show subpopulations

Gnomad AFR exome

AF:

0.000560

Gnomad AMR exome

AF:

0.0250

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0390

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.0148

Gnomad NFE exome

AF:

0.000399

Gnomad OTH exome

AF:

0.00540

GnomAD4 exome

AF:

0.00276

AC:

4036

AN:

1461462

Hom.:

Cov.:

AF XY:

0.00264

AC XY:

1916

AN XY:

727002

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.0237

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0437

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.0137

Gnomad4 NFE exome

AF:

0.000210

Gnomad4 OTH exome

AF:

0.00389

GnomAD4 genome

AF:

0.00396

AC:

603

AN:

152376

Hom.:

Cov.:

AF XY:

0.00518

AC XY:

386

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0399

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0174

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00103

Hom.:

Bravo

AF:

0.00424

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.6

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over