Genetic Variant RBMX:c.*606_*607insTTCATATGAGAGTTAC (chrX-136874453-C-CGTAACTCTCATATGAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_002139.4(RBMX):c.866-2_866-1insTTCATATGAGAGTTAC variant causes a splice acceptor, intron change involving the alteration of a conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

RBMX
NM_002139.4 splice_acceptor, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.89

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

syndromic X-linked intellectual disability Shashi type
Inheritance: Unknown, XL Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

RBMX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RBMX	NM_002139.4	MANE Select	c.866-2_866-1insTTCATATGAGAGTTAC	splice_acceptor intron	N/A	NP_002130.2	P38159-1
RBMX	NM_001164803.2		c.540+632_540+633insTTCATATGAGAGTTAC	intron	N/A	NP_001158275.1	P38159-3
RBMX	NR_028476.2		n.849-2_849-1insTTCATATGAGAGTTAC	splice_acceptor intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RBMX	ENST00000562646.5	TSL:1	c.606_607insTTCATATGAGAGTTAC	3_prime_UTR	Exon 8 of 8	ENSP00000457051.1	H3BT71
RBMX	ENST00000320676.11	TSL:1 MANE Select	c.866-2_866-1insTTCATATGAGAGTTAC	splice_acceptor intron	N/A	ENSP00000359645.3	P38159-1
RBMX	ENST00000568578.5	TSL:1	n.1088_1089insTTCATATGAGAGTTAC	non_coding_transcript_exon	Exon 7 of 8	ENSP00000457691.1	H3BR27

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

112052

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

9.22e-7

AC:

AN:

1084901

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

356773

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

26033

American (AMR)

AF:

0.00

AC:

AN:

34695

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18961

East Asian (EAS)

AF:

0.00

AC:

AN:

29715

South Asian (SAS)

AF:

0.00

AC:

AN:

53443

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39639

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4075

European-Non Finnish (NFE)

AF:

0.00000120

AC:

AN:

832969

Other (OTH)

AF:

0.00

AC:

AN:

45371

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

112109

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34915

African (AFR)

AF:

0.00

AC:

AN:

30998

American (AMR)

AF:

0.00

AC:

AN:

10647

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2633

East Asian (EAS)

AF:

0.00

AC:

AN:

3599

South Asian (SAS)

AF:

0.00

AC:

AN:

2782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6170

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52851

Other (OTH)

AF:

0.00

AC:

AN:

1541

Alfa

AF:

0.000297

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

7.9

Mutation Taster

=58/42

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over