X-136872325-A-AT

Variant names:

• chrX-136872325-A-AT
• ENST00000568578.5:n.*3216dupA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001164803.2(RBMX):​c.560dupA​(p.Tyr187fs) variant causes a frameshift, stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 22)
• Consequence: RBMX NM_001164803.2 frameshift, stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.718
• Publications: 0 publications found

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]

RBMX Gene-Disease associations (from GenCC):

• syndromic X-linked intellectual disability Shashi type

  Inheritance: Unknown, XL Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164803.2. 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
	RBMX	NM_001164803.2		c.560dupA	p.Tyr187fs	frameshift stop_gained	Exon 7 of 8	NP_001158275.1	P38159-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMX	ENST00000568578.5	TSL:1	n.*3216dupA		non_coding_transcript_exon	Exon 7 of 8	ENSP00000457691.1	H3BR27
	RBMX	ENST00000568578.5	TSL:1	n.*3216dupA		3_prime_UTR	Exon 7 of 8	ENSP00000457691.1	H3BR27
	RBMX	ENST00000431446.7	TSL:2	c.560dupA	p.Tyr187fs	frameshift stop_gained	Exon 7 of 8	ENSP00000411989.3	P38159-3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Severe X-linked intellectual disability, Gustavson type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.72

Splicing

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

Other links and lift over

hg19: chrX-135954484;