Genetic Variant RPL23:p.Val94Met (chr17-38850422-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_000978.4(RPL23):c.280G>A(p.Val94Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,613,882 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 1 hom. )

Consequence

RPL23
NM_000978.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 7.90

Publications

2 publications found

Variant links:

Genes affected

RPL23 (HGNC:10316): (ribosomal protein L23) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L14P family of ribosomal proteins. It is located in the cytoplasm. This gene has been referred to as rpL17 because the encoded protein shares amino acid identity with ribosomal protein L17 from Saccharomyces cerevisiae; however, its official symbol is RPL23. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPL23 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05338809).

BP6

Variant 17-38850422-C-T is Benign according to our data. Variant chr17-38850422-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1338129.

BS2

High AC in GnomAd4 at 38 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000978.4. 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
	RPL23	NM_000978.4	MANE Select	c.280G>A	p.Val94Met	missense	Exon 4 of 5	NP_000969.1	P62829

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL23	ENST00000479035.7	TSL:1 MANE Select	c.280G>A	p.Val94Met	missense	Exon 4 of 5	ENSP00000420311.2	P62829
RPL23	ENST00000584912.5	TSL:1	n.2438G>A		non_coding_transcript_exon	Exon 3 of 3
RPL23	ENST00000929683.1		c.361G>A	p.Val121Met	missense	Exon 5 of 6	ENSP00000599742.1

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000374

AC:

AN:

251438

AF XY:

0.000339

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000391

AC:

572

AN:

1461684

Hom.:

Cov.:

AF XY:

0.000391

AC XY:

284

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33478

American (AMR)

AF:

0.000626

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5616

European-Non Finnish (NFE)

AF:

0.000412

AC:

458

AN:

1111984

Other (OTH)

AF:

0.000298

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

116

145

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:

0.000250

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0000963

AC:

AN:

41526

American (AMR)

AF:

0.000197

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000353

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.000443

Hom.:

Bravo

AF:

0.000295

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000313

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000474

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.011

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.86

PhyloP100

7.9

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.8

REVEL

Benign

0.20

Sift

Benign

0.11

Sift4G

Benign

0.30

Polyphen

0.52

Vest4

0.58

MVP

0.39

MPC

1.1

ClinPred

0.064

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.75

Mutation Taster

=69/31

polymorphism

(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