Variant chr15-55182206-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000260443.9(RSL24D1):c.438A>T(p.Glu146Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000285 in 1,604,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

RSL24D1
ENST00000260443.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56

Variant links:

Genes affected

RSL24D1 (HGNC:18479): (ribosomal L24 domain containing 1) This gene encodes a protein sharing a low level of sequence similarity with human ribosomal protein L24. Although this gene has been referred to as RPL24, L30, and 60S ribosomal protein L30 isolog in the sequence databases, it is distinct from the human genes officially named RPL24 (which itself has been referred to as ribosomal protein L30) and RPL30. The protein encoded by this gene localizes to the nucleolus and is thought to play a role in the biogenesis of the 60S ribosomal subunit. The precise function of this gene is currently unknown. This gene utilizes alternative polyadenylation signals and has multiple pseudogenes. [provided by RefSeq, Jul 2012]

RSL24D1 links:

RSL24D1 (HGNC:):

RSL24D1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18819991).

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSL24D1	NM_016304.3 linkuse as main transcript	c.438A>T	p.Glu146Asp	missense_variant	6/6	ENST00000260443.9	NP_057388.1	Q9UHA3A0A024R5U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSL24D1	ENST00000260443.9 linkuse as main transcript	c.438A>T	p.Glu146Asp	missense_variant	6/6	1	NM_016304.3	ENSP00000260443.4		Q9UHA3

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000206

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000104

AC:

AN:

250600

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135512

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000302

AC:

439

AN:

1452508

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

214

AN XY:

723280

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000388

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.000125

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000179

Hom.:

Bravo

AF:

0.000102

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 14, 2023

The c.438A>T (p.E146D) alteration is located in exon 6 (coding exon 6) of the RSL24D1 gene. This alteration results from a A to T substitution at nucleotide position 438, causing the glutamic acid (E) at amino acid position 146 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.081

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.0097

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-2.0

REVEL

Benign

0.18

Sift

Benign

0.038

Sift4G

Benign

0.12

Polyphen

0.98

Vest4

0.43

MutPred

0.21

Loss of ubiquitination at K143 (P = 0.0516);

MVP

0.33

MPC

0.26

ClinPred

0.47

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.64

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