rs2011584

Variant names:

• chrX-136879428-G-A
• rs2011584
• NM_002139.4:c.-1C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-136879428-G-A
• chrX-136879428-G-C
• chrX-136879428-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002139.4(RBMX):​c.-1C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000951 in 105,207 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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 0.0000095 (0 hom., 0 hem., cov: 21)
  • Exomes 𝑓: 0.0000030 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: RBMX NM_002139.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.962
• Publications: 10 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]

SNORD61 (HGNC:10218): (small nucleolar RNA, C/D box 61) Small nucleolar RNAs (snoRNAs) are small noncoding RNAs involved in RNA processing. Box C/D class snoRNAs are involved in site-specific 2-prime-O-ribose methylation of preribosomal RNA precursors. This snoRNA is located in an intron of the RNA binding motif protein, X-linked gene (RBMX). [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).

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.-1C>T		5_prime_UTR	Exon 2 of 9	NP_002130.2	P38159-1
	RBMX	NM_001164803.2		c.-1C>T		5_prime_UTR	Exon 2 of 8	NP_001158275.1	P38159-3
	RBMX	NR_028476.2		n.155C>T		non_coding_transcript_exon	Exon 2 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMX	ENST00000320676.11	TSL:1 MANE Select	c.-1C>T		5_prime_UTR	Exon 2 of 9	ENSP00000359645.3	P38159-1
	RBMX	ENST00000562646.5	TSL:1	c.-1C>T		5_prime_UTR	Exon 2 of 8	ENSP00000457051.1	H3BT71
	RBMX	ENST00000568578.5	TSL:1	n.-1C>T		non_coding_transcript_exon	Exon 2 of 8	ENSP00000457691.1	H3BR27

Frequencies

GnomAD3 genomes AF: 0.00000951 AC: 1 AN: 105207 Hom.: 0 Cov.: 21

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: 0.0000195

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000297 AC: 3 AN: 1010171 Hom.: 0 Cov.: 33 AF XY: 0.00000319 AC XY: 1 AN XY: 313761

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

African (AFR) AF: 0.00 AC: 0 AN: 23268

American (AMR) AF: 0.00 AC: 0 AN: 28680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17645

East Asian (EAS) AF: 0.00 AC: 0 AN: 28822

South Asian (SAS) AF: 0.00 AC: 0 AN: 47296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3670

European-Non Finnish (NFE) AF: 0.00000384 AC: 3 AN: 780479

Other (OTH) AF: 0.00 AC: 0 AN: 42363

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000951 AC: 1 AN: 105207 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 28653

African (AFR) AF: 0.00 AC: 0 AN: 28831

American (AMR) AF: 0.00 AC: 0 AN: 9761

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2542

East Asian (EAS) AF: 0.00 AC: 0 AN: 3393

South Asian (SAS) AF: 0.00 AC: 0 AN: 2432

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 229

European-Non Finnish (NFE) AF: 0.0000195 AC: 1 AN: 51370

Other (OTH) AF: 0.00 AC: 0 AN: 1406

Alfa AF: 0.00 Hom.: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.97
PhyloP100		0.96
PromoterAI		-0.012	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: rs2011584; hg19: chrX-135961587;