X-136876650-C-T

Variant names:

• chrX-136876650-C-T
• rs755202665
• NM_002139.4:c.394G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002139.4(RBMX):​c.394G>A​(p.Gly132Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000754 in 1,061,512 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G132C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000075 (0 hom. 1 hem.)
• Consequence: RBMX NM_002139.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.903
• Publications: 3 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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1515173).

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.394G>A	p.Gly132Ser	missense	Exon 5 of 9	NP_002130.2	P38159-1
	RBMX	NM_001164803.2		c.217-1065G>A		intron	N/A	NP_001158275.1	P38159-3
	RBMX	NR_028476.2		n.377G>A		non_coding_transcript_exon	Exon 4 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMX	ENST00000320676.11	TSL:1 MANE Select	c.394G>A	p.Gly132Ser	missense	Exon 5 of 9	ENSP00000359645.3	P38159-1
	RBMX	ENST00000562646.5	TSL:1	c.394G>A	p.Gly132Ser	missense	Exon 5 of 8	ENSP00000457051.1	H3BT71
	RBMX	ENST00000568578.5	TSL:1	n.222G>A		non_coding_transcript_exon	Exon 4 of 8	ENSP00000457691.1	H3BR27

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.00000642 AC: 1 AN: 155766 AF XY: 0.0000190

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000844

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000754 AC: 8 AN: 1061512 Hom.: 0 Cov.: 29 AF XY: 0.00000294 AC XY: 1 AN XY: 339666

African (AFR) AF: 0.00 AC: 0 AN: 24377

American (AMR) AF: 0.00 AC: 0 AN: 27011

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17640

East Asian (EAS) AF: 0.0000675 AC: 2 AN: 29618

South Asian (SAS) AF: 0.0000204 AC: 1 AN: 49042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39577

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3947

European-Non Finnish (NFE) AF: 0.00000484 AC: 4 AN: 825921

Other (OTH) AF: 0.0000225 AC: 1 AN: 44379

GnomAD4 genome Cov.: 21

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.093	T
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.73	N
PhyloP100		0.90
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.20
Sift	Benign	0.11	T
Sift4G	Benign	0.13	T
Polyphen		0.12	B
Vest4		0.19
MutPred		0.30		Gain of phosphorylation at G132 (P = 0.0208)
MVP		0.79
MPC		1.3
ClinPred		0.10	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.25
gMVP		0.53
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs755202665; hg19: chrX-135958809; COSMIC: COSV57807978; COSMIC: COSV57807978;