X-130412804-C-A

Variant names:

• chrX-130412804-C-A
• rs775931625
• NM_016024.4:c.925C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_016024.4(RBMX2):​c.925C>A​(p.Arg309Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,097,057 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: 21)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: RBMX2 NM_016024.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640
• Publications: 0 publications found

Genes affected

RBMX2 (HGNC:24282): (RNA binding motif protein X-linked 2) Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nucleus. Part of U2-type precatalytic spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-0.64 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016024.4. 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
	RBMX2	NM_016024.4	MANE Select	c.925C>A	p.Arg309Arg	synonymous	Exon 6 of 6	NP_057108.2	Q9Y388

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMX2	ENST00000305536.11	TSL:1 MANE Select	c.925C>A	p.Arg309Arg	synonymous	Exon 6 of 6	ENSP00000339090.4	Q9Y388
	RBMX2	ENST00000919759.1		c.922C>A	p.Arg308Arg	synonymous	Exon 6 of 6	ENSP00000589818.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1097057 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 362731

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26347

American (AMR) AF: 0.00 AC: 0 AN: 35122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19357

East Asian (EAS) AF: 0.00 AC: 0 AN: 30198

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40513

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3595

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841909

Other (OTH) AF: 0.00 AC: 0 AN: 46012

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.2
DANN	Benign	0.48
PhyloP100		-0.64

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: rs775931625; hg19: chrX-129546778;