X-130412483-C-T

Variant names:

• chrX-130412483-C-T
• NM_016024.4:c.604C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_016024.4(RBMX2):​c.604C>T​(p.Pro202Ser) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P202L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 20)
• Consequence: RBMX2 NM_016024.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0380
• Publications: 0 publications found

Genes affected

RBMX2 (HGNC:24282): (RNA binding motif protein X-linked 2) Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nucleus. Part of U2-type precatalytic spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035750806).
• BP6: Variant X-130412483-C-T is Benign according to our data. Variant chrX-130412483-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3152495.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016024.4. 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
	RBMX2	NM_016024.4	MANE Select	c.604C>T	p.Pro202Ser	missense	Exon 6 of 6	NP_057108.2	Q9Y388

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMX2	ENST00000305536.11	TSL:1 MANE Select	c.604C>T	p.Pro202Ser	missense	Exon 6 of 6	ENSP00000339090.4	Q9Y388
	RBMX2	ENST00000919759.1		c.601C>T	p.Pro201Ser	missense	Exon 6 of 6	ENSP00000589818.1
	RBMX2	ENST00000487274.1	TSL:2	n.*88C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 20

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.50
DEOGEN2	Benign	0.087	T
FATHMM_MKL	Benign	0.0021	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.038
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.035
Sift	Benign	0.73	T
Sift4G	Benign	0.76	T
Polyphen		0.010	B
Vest4		0.016
MutPred		0.25		Gain of phosphorylation at P202 (P = 0.0013)
MVP		0.22
MPC		0.36
ClinPred		0.014	T
GERP RS		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.027
gMVP		0.059
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chrX-129546457;