6-17282837-G-T

Position:

• chr6-17282837-G-T

Variant summary

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

The NM_001143942.2(RBM24):​c.201G>T​(p.Arg67Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RBM24 NM_001143942.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72

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 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	c.201G>T	p.Arg67Ser	missense_variant	2/4	ENST00000379052.10	NP_001137414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM24	ENST00000379052.10	c.201G>T	p.Arg67Ser	missense_variant	2/4	1	NM_001143942.2	ENSP00000368341.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Jan 08, 2024

The c.201G>T (p.R67S) alteration is located in exon 2 (coding exon 2) of the RBM24 gene. This alteration results from a G to T substitution at nucleotide position 201, causing the arginine (R) at amino acid position 67 to be replaced by a serine (S). 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	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T;T;.;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.99	D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.55	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.65	N;.;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-5.5	D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0040	D;T;D;D
Polyphen		0.036	B;.;.;D
Vest4		0.88
MutPred		0.57		Loss of methylation at K70 (P = 0.0613);.;.;.;
MVP		0.76
MPC		1.5
ClinPred		1.0	D
GERP RS		0.39
Varity_R		0.87
gMVP		0.83

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: chr6-17283068;