Genetic Variant RRS1:p.Glu29Lys (chr8-66429216-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015169.4(RRS1):c.85G>A(p.Glu29Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,612,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E29Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

RRS1
NM_015169.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.14

Publications

0 publications found

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:

RRS1-DT (HGNC:50465): (RRS1 divergent transcript)

RRS1-DT links:

LOC102724687 (HGNC:):

LOC102724687 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23276511).

BS2

High AC in GnomAd4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015169.4. 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
	RRS1	NM_015169.4	MANE Select	c.85G>A	p.Glu29Lys	missense	Exon 1 of 1	NP_055984.1	Q15050
	RRS1-DT	NR_040434.1		n.-239C>T		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RRS1	ENST00000320270.4	TSL:6 MANE Select	c.85G>A	p.Glu29Lys	missense	Exon 1 of 1	ENSP00000322396.2	Q15050
RRS1-DT	ENST00000659008.1		n.87+3068C>T		intron	N/A
RRS1-DT	ENST00000734543.1		n.116+3068C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000159

AC:

AN:

245736

AF XY:

0.000165

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000950

Gnomad NFE exome

AF:

0.000325

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.000222

AC:

324

AN:

1460404

Hom.:

Cov.:

AF XY:

0.000219

AC XY:

159

AN XY:

726430

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.00

AC:

AN:

86040

European-Finnish (FIN)

AF:

0.000169

AC:

AN:

53138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.000279

AC:

310

AN:

1111458

Other (OTH)

AF:

0.0000829

AC:

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000352

Hom.:

Bravo

AF:

0.0000756

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000173

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.024

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PhyloP100

9.1

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.6

REVEL

Benign

0.18

Sift

Benign

0.27

Sift4G

Benign

0.79

Polyphen

0.56

Vest4

0.44

MVP

0.30

MPC

0.79

ClinPred

0.17

GERP RS

6.2

PromoterAI

0.0068

Neutral

(source)

Varity_R

0.83

gMVP

0.49

Mutation Taster

=48/52

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over