X-136874453-C-CGTAACTCTCATATGAATCTCTGTAGGAACCTCCACT

Variant names:

• chrX-136874453-C-CGTAACTCTCATATGAATCTCTGTAGGAACCTCCACT
• rs1256966146
• ENST00000562646:c.*606_*607insAGTGGAGGTTCCTACAGAGATTCATATGAGAGTTAC

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_002139.4(RBMX):​c.866-2_866-1insAGTGGAGGTTCCTACAGAGATTCATATGAGAGTTAC variant causes a splice acceptor, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: RBMX NM_002139.4 splice_acceptor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.89

Genes affected

RBMX (HGNC:9910): (RNA binding motif protein X-linked) This gene belongs to the RBMY gene family which includes candidate Y chromosome spermatogenesis genes. This gene, an active X chromosome homolog of the Y chromosome RBMY gene, is widely expressed whereas the RBMY gene evolved a male-specific function in spermatogenesis. Pseudogenes of this gene, found on chromosomes 1, 4, 9, 11, and 6, were likely derived by retrotransposition from the original gene. Alternatively spliced transcript variants encoding different isoforms have been identified. A snoRNA gene (SNORD61) is found in one of its introns. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease,
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBMX	NM_002139.4	c.866-2_866-1insAGTGGAGGTTCCTACAGAGATTCATATGAGAGTTAC		splice_acceptor_variant, intron_variant	Intron 8 of 8	ENST00000320676.11	NP_002130.2
RBMX	NM_001164803.2	c.540+632_540+633insAGTGGAGGTTCCTACAGAGATTCATATGAGAGTTAC		intron_variant	Intron 6 of 7		NP_001158275.1
RBMX	NR_028476.2	n.849-2_849-1insAGTGGAGGTTCCTACAGAGATTCATATGAGAGTTAC		splice_acceptor_variant, intron_variant	Intron 7 of 7
RBMX	NR_028477.2	n.1056-2_1056-1insAGTGGAGGTTCCTACAGAGATTCATATGAGAGTTAC		splice_acceptor_variant, intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMX	ENST00000320676.11	c.866-2_866-1insAGTGGAGGTTCCTACAGAGATTCATATGAGAGTTAC		splice_acceptor_variant, intron_variant	Intron 8 of 8	1	NM_002139.4	ENSP00000359645.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 22

Alfa AF: 0.000372 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1256966146; hg19: chrX-135956612;