X-136880723-G-A

Variant names:

• chrX-136880723-G-A
• rs1049604768
• NM_002139.4:c.-153C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_002139.4(RBMX):​c.-153C>T variant causes a 5 prime UTR premature start codon gain change. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., 1 hem., cov: 19)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: RBMX NM_002139.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.06
• 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: XL, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.11).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBMX	NM_002139.4	c.-153C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 9	ENST00000320676.11	NP_002130.2
RBMX	NM_002139.4	c.-153C>T		5_prime_UTR_variant	Exon 1 of 9	ENST00000320676.11	NP_002130.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMX	ENST00000320676.11	c.-153C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 9	1	NM_002139.4	ENSP00000359645.3
RBMX	ENST00000320676.11	c.-153C>T		5_prime_UTR_variant	Exon 1 of 9	1	NM_002139.4	ENSP00000359645.3

Frequencies

GnomAD3 genomes AF: 0.0000261 AC: 2 AN: 76487 Hom.: 0 Cov.: 19

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: 0.0000524

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 2161 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 327

African (AFR) AF: 0.00 AC: 0 AN: 1

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2121

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 24

Other (OTH) AF: 0.00 AC: 0 AN: 13

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000261 AC: 2 AN: 76487 Hom.: 0 Cov.: 19 AF XY: 0.0000592 AC XY: 1 AN XY: 16891

African (AFR) AF: 0.00 AC: 0 AN: 19349

American (AMR) AF: 0.00 AC: 0 AN: 6775

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1934

East Asian (EAS) AF: 0.00 AC: 0 AN: 2721

South Asian (SAS) AF: 0.00 AC: 0 AN: 1754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4149

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 199

European-Non Finnish (NFE) AF: 0.0000524 AC: 2 AN: 38132

Other (OTH) AF: 0.00 AC: 0 AN: 996

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Benign	0.97
PhyloP100		4.1
PromoterAI		0.028	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1049604768; hg19: chrX-135962882;