X-136874427-T-G

Variant names:

• chrX-136874427-T-G
• rs150079822
• NM_002139.4:c.891A>C
• RBMX p.Thr297Thr

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002139.4(RBMX):​c.891A>C​(p.Thr297Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T297T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 26)
• Consequence: RBMX NM_002139.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21
• 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: XL, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=2.21 with no splicing effect.

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.891A>C	p.Thr297Thr	synonymous	Exon 9 of 9	NP_002130.2	P38159-1
	RBMX	NM_001164803.2		c.540+659A>C		intron	N/A	NP_001158275.1	P38159-3
	RBMX	NR_028476.2		n.874A>C		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMX	ENST00000320676.11	TSL:1 MANE Select	c.891A>C	p.Thr297Thr	synonymous	Exon 9 of 9	ENSP00000359645.3	P38159-1
	RBMX	ENST00000562646.5	TSL:1	c.*633A>C		3_prime_UTR	Exon 8 of 8	ENSP00000457051.1	H3BT71
	RBMX	ENST00000568578.5	TSL:1	n.*1115A>C		non_coding_transcript_exon	Exon 7 of 8	ENSP00000457691.1	H3BR27

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD2 exomes AF: 0.00000620 AC: 1 AN: 161359 AF XY: 0.0000183

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000147

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		2.2
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs150079822;

hg19: chrX-135956586;