6-17292003-C-G

Position:

• chr6-17292003-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000379052.10(RBM24):​c.595C>G​(p.Gln199Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM24 ENST00000379052.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.37

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21070129).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM24	NM_001143942.2	c.595C>G	p.Gln199Glu	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	c.595C>G	p.Gln199Glu	missense_variant	4/4	1	NM_001143942.2	ENSP00000368341	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2023

The c.595C>G (p.Q199E) 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 595, causing the glutamine (Q) at amino acid position 199 to be replaced by a glutamic acid (E). 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	0.18
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.013	T;.;.
Eigen	Benign	0.042
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.75	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.051	T;D;D
Sift4G	Benign	0.26	T;T;T
Polyphen		0.61	P;.;B
Vest4		0.43
MutPred		0.39		Loss of helix (P = 0.0376);.;.;
MVP		0.47
MPC		0.86
ClinPred		0.53	D
GERP RS		4.8
Varity_R		0.21
gMVP		0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-17292234;