ENST00000562646.5:c.*606_*607insTGAGAGTTAT

Variant names:

• chrX-136874453-C-CATAACTCTCA
• rs1256966146
• ENST00000562646.5:c.*606_*607insTGAGAGTTAT

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The ENST00000562646.5(RBMX):​c.*606_*607insTGAGAGTTAT variant causes a 3 prime UTR change involving the alteration of a conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: RBMX ENST00000562646.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.89
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000562646.5. 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
	RBMX	NM_002139.4	MANE Select	c.866-2_866-1insTGAGAGTTAT		splice_acceptor intron	N/A	NP_002130.2	P38159-1
	RBMX	NM_001164803.2		c.540+632_540+633insTGAGAGTTAT		intron	N/A	NP_001158275.1	P38159-3
	RBMX	NR_028476.2		n.849-2_849-1insTGAGAGTTAT		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_*607insTGAGAGTTAT		3_prime_UTR	Exon 8 of 8	ENSP00000457051.1	H3BT71
	RBMX	ENST00000320676.11	TSL:1 MANE Select	c.866-2_866-1insTGAGAGTTAT		splice_acceptor intron	N/A	ENSP00000359645.3	P38159-1
	RBMX	ENST00000568578.5	TSL:1	n.*1088_*1089insTGAGAGTTAT		non_coding_transcript_exon	Exon 7 of 8	ENSP00000457691.1	H3BR27

Frequencies

GnomAD3 genomes AF: 0.00000895 AC: 1 AN: 111783 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000325

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1084714 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 356398

African (AFR) AF: 0.00 AC: 0 AN: 25990

American (AMR) AF: 0.00 AC: 0 AN: 34642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18979

East Asian (EAS) AF: 0.00 AC: 0 AN: 29516

South Asian (SAS) AF: 0.00 AC: 0 AN: 53434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39625

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4075

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 833099

Other (OTH) AF: 0.00 AC: 0 AN: 45354

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000894 AC: 1 AN: 111834 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 34756

⚠️ 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: 30852

American (AMR) AF: 0.00 AC: 0 AN: 10622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2630

East Asian (EAS) AF: 0.00 AC: 0 AN: 3584

South Asian (SAS) AF: 0.00 AC: 0 AN: 2767

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52799

Other (OTH) AF: 0.00 AC: 0 AN: 1534

⚠️ 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.

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;