X-136879428-G-T

Position:

• chrX-136879428-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BP6_Very_Strong

The NM_002139.4(RBMX):​c.-1C>A variant causes a 5 prime UTR 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 NM_002139.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.962

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RBMX	NM_002139.4	c.-1C>A		5_prime_UTR_variant	2/9	ENST00000320676.11	NP_002130.2
RBMX	NM_001164803.2	c.-1C>A		5_prime_UTR_variant	2/8		NP_001158275.1
RBMX	NR_028476.2	n.155C>A		non_coding_transcript_exon_variant	2/8
RBMX	NR_028477.2	n.155C>A		non_coding_transcript_exon_variant	2/9

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.730 AC: 76670 AN: 105039 Hom.: 19906 Cov.: 21 AF XY: 0.749 AC XY: 21368 AN XY: 28533

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

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

Gnomad4 AFR exome AF: 0.477

Gnomad4 AMR exome AF: 0.535

Gnomad4 ASJ exome AF: 0.473

Gnomad4 EAS exome AF: 0.491

Gnomad4 SAS exome AF: 0.353

Gnomad4 FIN exome AF: 0.543

Gnomad4 NFE exome AF: 0.513

Gnomad4 OTH exome AF: 0.495

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

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.792

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.799

Gnomad4 NFE AF: 0.749

Gnomad4 OTH AF: 0.727

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Benign	0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs2011584; hg19: chrX-135961587; COSMIC: COSV100285032; COSMIC: COSV100285032;