X-130412483-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 14/20 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

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

Verdict is Likely_benign. Variant got -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 id is 3152495.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBMX2	NM_016024.4	c.604C>T	p.Pro202Ser	missense_variant	Exon 6 of 6	ENST00000305536.11	NP_057108.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMX2	ENST00000305536.11	c.604C>T	p.Pro202Ser	missense_variant	Exon 6 of 6	1	NM_016024.4	ENSP00000339090.4
RBMX2	ENST00000487274.1	n.*88C>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 20

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 03, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.036	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L;.
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);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-129546457;