6-17291880-G-A

Position:

• chr6-17291880-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001143942.2(RBM24):​c.472G>A​(p.Ala158Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000328 in 1,461,684 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: 0.000033 (0 hom.)
• Consequence: RBM24 NM_001143942.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.71

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 48 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM24	NM_001143942.2	c.472G>A	p.Ala158Thr	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.472G>A	p.Ala158Thr	missense_variant	4/4	1	NM_001143942.2	ENSP00000368341.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000328 AC: 48 AN: 1461684 Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 26 AN XY: 727150

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000414

Gnomad4 OTH exome AF: 0.0000331

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

Sep 20, 2023

The c.472G>A (p.A158T) alteration is located in exon 4 (coding exon 4) of the RBM24 gene. This alteration results from a G to A substitution at nucleotide position 472, causing the alanine (A) at amino acid position 158 to be replaced by a threonine (T). 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	0.10
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T;.;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.42	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.2	L;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.86	N;N;N
REVEL	Benign	0.17
Sift	Benign	0.21	T;T;T
Sift4G	Benign	0.34	T;T;T
Polyphen		1.0	D;.;D
Vest4		0.51
MutPred		0.41		Gain of loop (P = 0.0051);.;.;
MVP		0.88
MPC		1.7
ClinPred		0.88	D
GERP RS		5.7
Varity_R		0.13
gMVP		0.75

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

Other links and lift over

dbSNP: rs1760371760; hg19: chr6-17292111;