chrX-48575250-G-A

Position:

• chrX-48575250-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_006743.5(RBM3):​c.70G>A​(p.Asp24Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000365 in 1,096,646 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000036 (0 hom. 2 hem.)
• Consequence: RBM3 NM_006743.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.45

Genes affected

RBM3 (HGNC:9900): (RNA binding motif protein 3) This gene is a member of the glycine-rich RNA-binding protein family and encodes a protein with one RNA recognition motif (RRM) domain. Expression of this gene is induced by cold shock and low oxygen tension. A pseudogene exists on chromosome 1. Multiple alternatively spliced transcript variants that are predicted to encode different isoforms have been characterized although some of these variants fit nonsense-mediated decay (NMD) criteria. [provided by RefSeq, Jul 2008]

RBM3 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.40688577).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM3	NM_006743.5	c.70G>A	p.Asp24Asn	missense_variant	2/7	ENST00000376759.8	NP_006734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM3	ENST00000376759.8	c.70G>A	p.Asp24Asn	missense_variant	2/7	1	NM_006743.5	ENSP00000365950.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000365 AC: 4 AN: 1096646 Hom.: 0 Cov.: 30 AF XY: 0.00000552 AC XY: 2 AN XY: 362060

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: 0.00000476

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

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

Oct 09, 2024

The c.70G>A (p.D24N) alteration is located in exon 2 (coding exon 1) of the RBM3 gene. This alteration results from a G to A substitution at nucleotide position 70, causing the aspartic acid (D) at amino acid position 24 to be replaced by an asparagine (N). 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	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Uncertain	-0.096	T
MutationAssessor	Benign	0.33	N;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.7	N;N
REVEL	Uncertain	0.34
Sift	Benign	0.11	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.97	D;D
Vest4		0.25
MutPred		0.39		Gain of catalytic residue at E23 (P = 0.1715);Gain of catalytic residue at E23 (P = 0.1715);
MVP		0.92
MPC		1.6
ClinPred		0.81	D
GERP RS		3.8
Varity_R		0.18
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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-48433638;