GeneBe

X-136874453-C-CGTAACTCTCATATGAA

Variant names:

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1

The NM_002139.4(RBMX):​c.866-2_866-1insTTCATATGAGAGTTAC variant causes a splice acceptor, intron 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 0.0 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control

Consequence

RBMX
NM_002139.4 splice_acceptor, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.89
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease,

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RBMXNM_002139.4 linkc.866-2_866-1insTTCATATGAGAGTTAC splice_acceptor_variant, intron_variant Intron 8 of 8 ENST00000320676.11 NP_002130.2 P38159-1
RBMXNM_001164803.2 linkc.540+632_540+633insTTCATATGAGAGTTAC intron_variant Intron 6 of 7 NP_001158275.1 P38159-3
RBMXNR_028476.2 linkn.849-2_849-1insTTCATATGAGAGTTAC splice_acceptor_variant, intron_variant Intron 7 of 7
RBMXNR_028477.2 linkn.1056-2_1056-1insTTCATATGAGAGTTAC splice_acceptor_variant, intron_variant Intron 8 of 8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RBMXENST00000320676.11 linkc.866-2_866-1insTTCATATGAGAGTTAC splice_acceptor_variant, intron_variant Intron 8 of 8 1 NM_002139.4 ENSP00000359645.3 P38159-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
112052
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
34854
FAILED QC
Gnomad AFR
AF:
0.00
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: AS_VQSR
AF:
9.22e-7
AC:
1
AN:
1084901
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
356773
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000120
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
112109
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
34915
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000297
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1256966146; hg19: chrX-135956612; API