X-136879428-G-T

Variant names:

• chrX-136879428-G-T
• rs2011584
• ENST00000568578.5:n.-1C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BP6_Very_Strong

The ENST00000568578.5(RBMX):​n.-1C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (19904 hom., 21394 hem., cov: 21)
  • Exomes 𝑓: 0.51 (31139 hom. 67269 hem.)
  • Failed GnomAD Quality Control
• Consequence: RBMX ENST00000568578.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant X-136879428-G-T is Benign according to our data. Variant chrX-136879428-G-T is described in ClinVar as [Benign]. Clinvar id is 1327942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMX	ENST00000320676.11	c.-1C>A		5_prime_UTR_variant	Exon 2 of 9	1	NM_002139.4	ENSP00000359645.3

Frequencies

GnomAD3 genomes AF: 0.730 AC: 76670 AN: 105039 Hom.: 19906 Cov.: 21

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.629

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.730

GnomAD2 exomes AF: 0.525 AC: 54902 AN: 104674 AF XY: 0.838

Gnomad AFR exome AF: 0.505

Gnomad AMR exome AF: 0.522

Gnomad ASJ exome AF: 0.516

Gnomad EAS exome AF: 0.503

Gnomad FIN exome AF: 0.547

Gnomad NFE exome AF: 0.532

Gnomad OTH exome AF: 0.519

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.505 AC: 423602 AN: 838594 Hom.: 31139 Cov.: 33 AF XY: 0.470 AC XY: 67269 AN XY: 143158

African (AFR) AF: 0.477 AC: 9653 AN: 20245

American (AMR) AF: 0.535 AC: 12856 AN: 24046

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 6866 AN: 14521

East Asian (EAS) AF: 0.491 AC: 11559 AN: 23537

South Asian (SAS) AF: 0.353 AC: 12508 AN: 35432

European-Finnish (FIN) AF: 0.543 AC: 16885 AN: 31095

Middle Eastern (MID) AF: 0.462 AC: 1414 AN: 3059

European-Non Finnish (NFE) AF: 0.513 AC: 334238 AN: 651084

Other (OTH) AF: 0.495 AC: 17623 AN: 35575

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.730 AC: 76690 AN: 105047 Hom.: 19904 Cov.: 21 AF XY: 0.749 AC XY: 21394 AN XY: 28555

African (AFR) AF: 0.682 AC: 19648 AN: 28822

American (AMR) AF: 0.792 AC: 7728 AN: 9756

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 1786 AN: 2539

East Asian (EAS) AF: 0.736 AC: 2486 AN: 3380

South Asian (SAS) AF: 0.585 AC: 1416 AN: 2419

European-Finnish (FIN) AF: 0.799 AC: 3651 AN: 4568

Middle Eastern (MID) AF: 0.639 AC: 133 AN: 208

European-Non Finnish (NFE) AF: 0.749 AC: 38425 AN: 51279

Other (OTH) AF: 0.727 AC: 1031 AN: 1419

Alfa AF: 0.00218 Hom.: 3

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Syndromic X-linked intellectual disability Shashi type Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Benign	0.91
PhyloP100		0.96
PromoterAI		-0.0043	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV100285032; COSMIC: COSV100285032;