Genetic Variant RBMX:c.-1C>A (chrX-136879428-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBP6_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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.962

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]

RBMX links:

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]

SNORD61 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
RBMX	NM_002139.4 link	c.-1C>A		5_prime_UTR_variant	Exon 2 of 9	ENST00000320676.11	NP_002130.2	P38159-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMX	ENST00000320676.11 link	c.-1C>A		5_prime_UTR_variant	Exon 2 of 9	1	NM_002139.4	ENSP00000359645.3		P38159-1

Frequencies

GnomAD3 genomes

AF:

0.730

AC:

76670

AN:

105039

Hom.:

19906

Cov.:

AF XY:

0.749

AC XY:

21368

AN XY:

28533

show subpopulations

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.:

AF XY:

0.470

AC XY:

67269

AN XY:

143158

show subpopulations

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.:

AF XY:

0.749

AC XY:

21394

AN XY:

28555

show subpopulations

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.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over