X-130402255-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_016024.4(RBMX2):​c.6C>T​(p.Asn2Asn) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,023,508 control chromosomes in the GnomAD database, including 1 homozygotes. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 18)
Exomes 𝑓: 0.000011 ( 1 hom. 2 hem. )

Consequence

RBMX2
NM_016024.4 splice_region, synonymous

Scores

2
Splicing: ADA: 0.001205
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.16
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 -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
Variant X-130402255-C-T is Benign according to our data. Variant chrX-130402255-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2610596.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.16 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RBMX2NM_016024.4 linkc.6C>T p.Asn2Asn splice_region_variant, synonymous_variant Exon 2 of 6 ENST00000305536.11 NP_057108.2 Q9Y388

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RBMX2ENST00000305536.11 linkc.6C>T p.Asn2Asn splice_region_variant, synonymous_variant Exon 2 of 6 1 NM_016024.4 ENSP00000339090.4 Q9Y388
RBMX2ENST00000469953.1 linkn.255C>T non_coding_transcript_exon_variant Exon 1 of 4 1
RBMX2ENST00000370947.1 linkc.6C>T p.Asn2Asn splice_region_variant, synonymous_variant Exon 2 of 3 2 ENSP00000359985.1 Q5JY83

Frequencies

GnomAD3 genomes
Cov.:
18
GnomAD3 exomes
AF:
0.00000592
AC:
1
AN:
168873
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
56679
show subpopulations
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 SAS exome
AF:
0.0000597
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000107
AC:
11
AN:
1023508
Hom.:
1
Cov.:
43
AF XY:
0.00000618
AC XY:
2
AN XY:
323696
show subpopulations
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:
0.000194
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000126
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
18

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jul 11, 2023
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
BayesDel_noAF
Benign
-0.65
CADD
Benign
12
DANN
Benign
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0012
dbscSNV1_RF
Benign
0.070
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: rs768008291; hg19: chrX-129536229; API