X-130412468-A-G

Variant names:

• chrX-130412468-A-G
• NM_016024.4:c.589A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016024.4(RBMX2):​c.589A>G​(p.Lys197Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,098,075 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000027 (0 hom. 1 hem.)
• Consequence: RBMX2 NM_016024.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12296167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBMX2	NM_016024.4	c.589A>G	p.Lys197Glu	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.589A>G	p.Lys197Glu	missense_variant	Exon 6 of 6	1	NM_016024.4	ENSP00000339090.4
RBMX2	ENST00000487274.1	n.*73A>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1098075 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 1 AN XY: 363525

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000356

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.589A>G (p.K197E) alteration is located in exon 6 (coding exon 6) of the RBMX2 gene. This alteration results from a A to G substitution at nucleotide position 589, causing the lysine (K) at amino acid position 197 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;.
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.6	N;.
REVEL	Benign	0.026
Sift	Uncertain	0.0020	D;.
Sift4G	Benign	0.32	T;.
Polyphen		0.012	B;.
Vest4		0.24
MutPred		0.36		Loss of methylation at K197 (P = 0.003);Loss of methylation at K197 (P = 0.003);
MVP		0.37
MPC		0.54
ClinPred		0.21	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.27
gMVP		0.15

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-129546442;