chrX-136874453-C-CGTAACTCTCATA

Variant names:

• chrX-136874453-C-CGTAACTCTCATA
• rs1256966146
• ENST00000562646.5:c.*606_*607insTATGAGAGTTAC

Variant summary

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

The NM_002139.4(RBMX):​c.866-2_866-1insTATGAGAGTTAC variant causes a splice acceptor, intron change involving the alteration of a conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.000012 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: RBMX NM_002139.4 splice_acceptor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.89
• Publications: 1 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 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002139.4. 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
	RBMX	NM_002139.4	MANE Select	c.866-2_866-1insTATGAGAGTTAC		splice_acceptor intron	N/A	NP_002130.2	P38159-1
	RBMX	NM_001164803.2		c.540+632_540+633insTATGAGAGTTAC		intron	N/A	NP_001158275.1	P38159-3
	RBMX	NR_028476.2		n.849-2_849-1insTATGAGAGTTAC		splice_acceptor intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMX	ENST00000562646.5	TSL:1	c.*606_*607insTATGAGAGTTAC		3_prime_UTR	Exon 8 of 8	ENSP00000457051.1	H3BT71
	RBMX	ENST00000320676.11	TSL:1 MANE Select	c.866-2_866-1insTATGAGAGTTAC		splice_acceptor intron	N/A	ENSP00000359645.3	P38159-1
	RBMX	ENST00000568578.5	TSL:1	n.*1088_*1089insTATGAGAGTTAC		non_coding_transcript_exon	Exon 7 of 8	ENSP00000457691.1	H3BR27

Frequencies

GnomAD3 genomes AF: 0.0000448 AC: 5 AN: 111574 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000163

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000571

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 182765 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000121 AC: 13 AN: 1077349 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 352011

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

African (AFR) AF: 0.0000387 AC: 1 AN: 25841

American (AMR) AF: 0.00 AC: 0 AN: 34426

Ashkenazi Jewish (ASJ) AF: 0.0000534 AC: 1 AN: 18732

East Asian (EAS) AF: 0.00 AC: 0 AN: 29715

South Asian (SAS) AF: 0.00 AC: 0 AN: 52987

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39215

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4050

European-Non Finnish (NFE) AF: 0.0000133 AC: 11 AN: 827410

Other (OTH) AF: 0.00 AC: 0 AN: 44973

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0000448 AC: 5 AN: 111628 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 34668

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

African (AFR) AF: 0.0000324 AC: 1 AN: 30889

American (AMR) AF: 0.00 AC: 0 AN: 10631

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2615

East Asian (EAS) AF: 0.00 AC: 0 AN: 3599

South Asian (SAS) AF: 0.00 AC: 0 AN: 2782

European-Finnish (FIN) AF: 0.000163 AC: 1 AN: 6138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.0000571 AC: 3 AN: 52553

Other (OTH) AF: 0.00 AC: 0 AN: 1536

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00134 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.9
Mutation Taster		=54/46	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1256966146; hg19: chrX-135956612;