X-136874321-C-G

Variant names:

• chrX-136874321-C-G
• rs148934011
• NM_002139.4:c.997G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002139.4(RBMX):​c.997G>C​(p.Asp333His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RBMX NM_002139.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.02

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBMX	NM_002139.4	c.997G>C	p.Asp333His	missense_variant	Exon 9 of 9	ENST00000320676.11	NP_002130.2
RBMX	NM_001164803.2	c.540+765G>C		intron_variant	Intron 6 of 7		NP_001158275.1
RBMX	NR_028476.2	n.980G>C		non_coding_transcript_exon_variant	Exon 8 of 8
RBMX	NR_028477.2	n.1187G>C		non_coding_transcript_exon_variant	Exon 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMX	ENST00000320676.11	c.997G>C	p.Asp333His	missense_variant	Exon 9 of 9	1	NM_002139.4	ENSP00000359645.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 87

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Pathogenic	0.56	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Uncertain	0.36	D
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Uncertain	0.62
Sift	Benign	0.064	T;D
Sift4G	Benign	0.073	T;D
Polyphen		1.0	D;.
Vest4		0.54
MutPred		0.33		Gain of sheet (P = 0.0125);.;
MVP		0.93
MPC		2.7
ClinPred		0.98	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.79
gMVP		0.66

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: rs148934011; hg19: chrX-135956480;