chrX-130412408-C-T

Variant names:

• chrX-130412408-C-T
• rs763675101
• NM_016024.4:c.529C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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. 14/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.189
• 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: Benign. The variant received -8 ACMG points.

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

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.529C>T	p.Arg177Trp	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.529C>T	p.Arg177Trp	missense	Exon 6 of 6	ENSP00000339090.4	Q9Y388
	RBMX2	ENST00000919759.1		c.526C>T	p.Arg176Trp	missense	Exon 6 of 6	ENSP00000589818.1
	RBMX2	ENST00000487274.1	TSL:2	n.*13C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0000278 AC: 3 AN: 107860 Hom.: 0 Cov.: 20

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

GnomAD2 exomes AF: 0.0000780 AC: 12 AN: 153801 AF XY: 0.0000966

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 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

African (AFR) AF: 0.0000410 AC: 1 AN: 24410

American (AMR) AF: 0.00 AC: 0 AN: 27542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17845

East Asian (EAS) AF: 0.00 AC: 0 AN: 29505

South Asian (SAS) AF: 0.000576 AC: 27 AN: 46907

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39741

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3938

European-Non Finnish (NFE) AF: 0.00000723 AC: 6 AN: 829682

Other (OTH) AF: 0.0000900 AC: 4 AN: 44445

GnomAD4 genome AF: 0.0000278 AC: 3 AN: 107860 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 30388

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29467

American (AMR) AF: 0.00 AC: 0 AN: 9962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2610

East Asian (EAS) AF: 0.00 AC: 0 AN: 3466

South Asian (SAS) AF: 0.000416 AC: 1 AN: 2405

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 232

European-Non Finnish (NFE) AF: 0.0000191 AC: 1 AN: 52230

Other (OTH) AF: 0.000696 AC: 1 AN: 1437

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000343967), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.0000416

ExAC AF: 0.0000910 AC: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.074
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
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.19
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
Mutation Taster		=95/5	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

dbSNP: rs763675101; hg19: chrX-129546382;