Variant chr6-17291760-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000379052.10(RBM24):c.352C>G(p.Pro118Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RBM24
ENST00000379052.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.75

Variant links:

Genes affected

RBM24 (HGNC:21539): (RNA binding motif protein 24) Enables mRNA 3'-UTR AU-rich region binding activity; mRNA CDS binding activity; and sequence-specific mRNA binding activity. Involved in several processes, including negative regulation of cytoplasmic translation; positive regulation of cell differentiation; and regulation of mRNA metabolic process. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RBM24 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM24	NM_001143942.2 linkuse as main transcript	c.352C>G	p.Pro118Ala	missense_variant	4/4	ENST00000379052.10	NP_001137414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM24	ENST00000379052.10 linkuse as main transcript	c.352C>G	p.Pro118Ala	missense_variant	4/4	1	NM_001143942.2	ENSP00000368341	P1	Q9BX46-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245898

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133390

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000558

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1452884

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721344

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 18, 2023

The c.352C>G (p.P118A) alteration is located in exon 4 (coding exon 4) of the RBM24 gene. This alteration results from a C to G substitution at nucleotide position 352, causing the proline (P) at amino acid position 118 to be replaced by an alanine (A). 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

Benign

0.33

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.071

T;.;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.1

L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-2.6

D;N;N

REVEL

Benign

0.24

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.17

T;T;T

Polyphen

0.011

B;.;B

Vest4

0.56

MutPred

0.50

Gain of catalytic residue at P118 (P = 0.0919);.;.;

MVP

0.92

MPC

0.69

ClinPred

0.43

GERP RS

5.6

Varity_R

0.20

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.38

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.38

Position offset: 1

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