NM_006743.5:c.-13-57C>G

Variant names:

• chrX-48575111-C-G
• rs2249583
• NM_006743.5:c.-13-57C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006743.5(RBM3):​c.-13-57C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 110,678 control chromosomes in the GnomAD database, including 9,715 homozygotes. There are 15,848 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: 𝑓 0.47 (9715 hom., 15848 hem., cov: 23)
  • Exomes 𝑓: 0.57 (90624 hom. 125167 hem.)
  • Failed GnomAD Quality Control
• Consequence: RBM3 NM_006743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 8 publications found

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]

ENSG00000204620 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006743.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM3	NM_006743.5	MANE Select	c.-13-57C>G		intron	N/A	NP_006734.1	P98179

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM3	ENST00000376759.8	TSL:1 MANE Select	c.-13-57C>G		intron	N/A	ENSP00000365950.3	P98179
	RBM3	ENST00000491240.5	TSL:1	n.51-57C>G		intron	N/A
	RBM3	ENST00000376755.1	TSL:2	c.-70C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000365946.1	P98179

Frequencies

GnomAD3 genomes AF: 0.475 AC: 52555 AN: 110627 Hom.: 9731 Cov.: 23

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.494

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.572 AC: 439090 AN: 767708 Hom.: 90624 Cov.: 12 AF XY: 0.584 AC XY: 125167 AN XY: 214212

African (AFR) AF: 0.228 AC: 4399 AN: 19321

American (AMR) AF: 0.579 AC: 16074 AN: 27774

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 11591 AN: 16817

East Asian (EAS) AF: 0.472 AC: 12541 AN: 26583

South Asian (SAS) AF: 0.571 AC: 25071 AN: 43943

European-Finnish (FIN) AF: 0.580 AC: 21447 AN: 36959

Middle Eastern (MID) AF: 0.606 AC: 2122 AN: 3504

European-Non Finnish (NFE) AF: 0.585 AC: 326058 AN: 557645

Other (OTH) AF: 0.563 AC: 19787 AN: 35162

GnomAD4 genome AF: 0.475 AC: 52542 AN: 110678 Hom.: 9715 Cov.: 23 AF XY: 0.481 AC XY: 15848 AN XY: 32926

African (AFR) AF: 0.231 AC: 7049 AN: 30552

American (AMR) AF: 0.544 AC: 5635 AN: 10352

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 1779 AN: 2630

East Asian (EAS) AF: 0.473 AC: 1644 AN: 3478

South Asian (SAS) AF: 0.545 AC: 1440 AN: 2643

European-Finnish (FIN) AF: 0.573 AC: 3338 AN: 5829

Middle Eastern (MID) AF: 0.587 AC: 125 AN: 213

European-Non Finnish (NFE) AF: 0.574 AC: 30322 AN: 52820

Other (OTH) AF: 0.495 AC: 740 AN: 1494

Alfa AF: 0.508 Hom.: 3654

Bravo AF: 0.465

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.54
DANN	Benign	0.52
PhyloP100		-1.9
PromoterAI		0.086	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.95
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2249583; hg19: chrX-48433499; COSMIC: COSV63202677; COSMIC: COSV63202677;