X-130412408-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016024.4(RBMX2):​c.529C>T​(p.Arg177Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000035 in 1,171,875 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 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: 𝑓 0.000028 ( 0 hom., 0 hem., cov: 20)
Exomes 𝑓: 0.000036 ( 0 hom. 18 hem. )

Consequence

RBMX2
NM_016024.4 missense

Scores

1
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.189
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.05023721).
BS2
High Hemizygotes in GnomAdExome4 at 18 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RBMX2NM_016024.4 linkc.529C>T p.Arg177Trp missense_variant Exon 6 of 6 ENST00000305536.11 NP_057108.2 Q9Y388

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RBMX2ENST00000305536.11 linkc.529C>T p.Arg177Trp missense_variant Exon 6 of 6 1 NM_016024.4 ENSP00000339090.4 Q9Y388
RBMX2ENST00000487274.1 linkn.*13C>T downstream_gene_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0000278
AC:
3
AN:
107860
Hom.:
0
Cov.:
20
AF XY:
0.00
AC XY:
0
AN XY:
30388
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000416
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000191
Gnomad OTH
AF:
0.000696
GnomAD3 exomes
AF:
0.0000780
AC:
12
AN:
153801
Hom.:
0
AF XY:
0.0000966
AC XY:
5
AN XY:
51737
show subpopulations
Gnomad AFR exome
AF:
0.000176
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000609
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000138
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000357
AC:
38
AN:
1064015
Hom.:
0
Cov.:
32
AF XY:
0.0000524
AC XY:
18
AN XY:
343813
show subpopulations
Gnomad4 AFR exome
AF:
0.0000410
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000576
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000723
Gnomad4 OTH exome
AF:
0.0000900
GnomAD4 genome
AF:
0.0000278
AC:
3
AN:
107860
Hom.:
0
Cov.:
20
AF XY:
0.00
AC XY:
0
AN XY:
30388
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000416
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000191
Gnomad4 OTH
AF:
0.000696
Alfa
AF:
0.000142
Hom.:
1
Bravo
AF:
0.0000416
ExAC
AF:
0.0000910
AC:
11

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 15, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.529C>T (p.R177W) alteration is located in exon 6 (coding exon 6) of the RBMX2 gene. This alteration results from a C to T substitution at nucleotide position 529, causing the arginine (R) at amino acid position 177 to be replaced by a tryptophan (W). 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
0.074
BayesDel_addAF
Benign
-0.69
T
BayesDel_noAF
Benign
-0.87
CADD
Benign
9.4
DANN
Benign
0.94
DEOGEN2
Uncertain
0.43
T;.
FATHMM_MKL
Benign
0.0080
N
LIST_S2
Benign
0.69
T;T
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.050
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.0
L;.
PrimateAI
Benign
0.23
T
PROVEAN
Uncertain
-3.4
D;.
REVEL
Benign
0.045
Sift
Uncertain
0.0010
D;.
Sift4G
Pathogenic
0.0010
D;.
Polyphen
0.0080
B;.
Vest4
0.085
MVP
0.082
MPC
0.38
ClinPred
0.25
T
GERP RS
0.34
Varity_R
0.075
gMVP
0.23

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs763675101; hg19: chrX-129546382; API