Genetic Variant RRS1:p.Asn267Tyr (chr8-66429930-A-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015169.4(RRS1):c.799A>T(p.Asn267Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00442 in 1,614,148 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 15 hom. )

Consequence

RRS1
NM_015169.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.40

Variant links:

Genes affected

RRS1 (HGNC:17083): (ribosome biogenesis regulator 1 homolog) Enables 5S rRNA binding activity. Involved in several processes, including mitotic metaphase plate congression; protein localization to nucleolus; and ribosomal large subunit assembly. Located in condensed nuclear chromosome; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RRS1 links:

ENSG00000287127 (HGNC:):

ENSG00000287127 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070470273).

BP6

Variant 8-66429930-A-T is Benign according to our data. Variant chr8-66429930-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 773505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 454 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRS1	NM_015169.4 link	c.799A>T	p.Asn267Tyr	missense_variant	Exon 1 of 1	ENST00000320270.4	NP_055984.1	Q15050

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRS1	ENST00000320270.4 link	c.799A>T	p.Asn267Tyr	missense_variant	Exon 1 of 1	6	NM_015169.4	ENSP00000322396.2		Q15050
ENSG00000287127	ENST00000659008.1 link	n.87+2354T>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00299

AC:

455

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00501

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00350

AC:

877

AN:

250640

Hom.:

AF XY:

0.00352

AC XY:

478

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.000745

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00258

Gnomad FIN exome

AF:

0.00245

Gnomad NFE exome

AF:

0.00582

Gnomad OTH exome

AF:

0.00311

GnomAD4 exome

AF:

0.00457

AC:

6675

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00449

AC XY:

3264

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00145

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00286

Gnomad4 FIN exome

AF:

0.00277

Gnomad4 NFE exome

AF:

0.00532

Gnomad4 OTH exome

AF:

0.00374

GnomAD4 genome

AF:

0.00298

AC:

454

AN:

152340

Hom.:

Cov.:

AF XY:

0.00268

AC XY:

200

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000841

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.00235

Gnomad4 NFE

AF:

0.00500

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00434

Hom.:

Bravo

AF:

0.00286

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00640

AC:

ExAC

AF:

0.00394

AC:

479

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00594

EpiControl

AF:

0.00433

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.082

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.78

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.0070

MetaSVM

Benign

-0.34

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.30

Sift

Benign

0.042

Sift4G

Uncertain

0.029

Polyphen

0.90

Vest4

0.14

MVP

0.87

MPC

0.89

ClinPred

0.086

GERP RS

4.1

Varity_R

0.22

gMVP

0.11

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