X-130412804-C-T

Variant names:

• chrX-130412804-C-T
• rs775931625
• NM_016024.4:c.925C>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.925C>T​(p.Arg309Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000324 in 1,208,368 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 130 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., 4 hem., cov: 21)
  • Exomes 𝑓: 0.00034 (0 hom. 126 hem.)
• Consequence: RBMX2 NM_016024.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.640
• Publications: 1 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=0.020367116).
• BS2: High Hemizygotes in GnomAd4 at 4 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.925C>T	p.Arg309Trp	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.925C>T	p.Arg309Trp	missense	Exon 6 of 6	ENSP00000339090.4	Q9Y388
	RBMX2	ENST00000919759.1		c.922C>T	p.Arg308Trp	missense	Exon 6 of 6	ENSP00000589818.1

Frequencies

GnomAD3 genomes AF: 0.000162 AC: 18 AN: 111259 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.0000980

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000191

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000383

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000226

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000245 AC: 44 AN: 179649 AF XY: 0.000225

Gnomad AFR exome AF: 0.000167

Gnomad AMR exome AF: 0.000440

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000336

Gnomad OTH exome AF: 0.000226

GnomAD4 exome AF: 0.000341 AC: 374 AN: 1097055 Hom.: 0 Cov.: 32 AF XY: 0.000347 AC XY: 126 AN XY: 362731

African (AFR) AF: 0.00 AC: 0 AN: 26347

American (AMR) AF: 0.000484 AC: 17 AN: 35122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19357

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30198

South Asian (SAS) AF: 0.000185 AC: 10 AN: 54004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40513

Middle Eastern (MID) AF: 0.000556 AC: 2 AN: 3595

European-Non Finnish (NFE) AF: 0.000393 AC: 331 AN: 841907

Other (OTH) AF: 0.000283 AC: 13 AN: 46012

GnomAD4 genome AF: 0.000153 AC: 17 AN: 111313 Hom.: 0 Cov.: 21 AF XY: 0.000119 AC XY: 4 AN XY: 33511

African (AFR) AF: 0.0000978 AC: 3 AN: 30671

American (AMR) AF: 0.000190 AC: 2 AN: 10511

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2641

East Asian (EAS) AF: 0.00 AC: 0 AN: 3509

South Asian (SAS) AF: 0.00 AC: 0 AN: 2601

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 213

European-Non Finnish (NFE) AF: 0.000226 AC: 12 AN: 52990

Other (OTH) AF: 0.00 AC: 0 AN: 1520

Alfa AF: 0.000304 Hom.: 2

Bravo AF: 0.000204

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000346 AC: 1

ExAC AF: 0.000290 AC: 35

EpiCase AF: 0.000491

EpiControl AF: 0.000237

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	0.084
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.16	T
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.64
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.013
Sift	Benign	0.085	T
Sift4G	Benign	0.15	T
Polyphen		0.0090	B
Vest4		0.040
MutPred		0.26		Loss of helix (P = 0.0376)
MVP		0.13
MPC		0.37
ClinPred		0.045	T
GERP RS		0.81
Varity_R		0.088
gMVP		0.19
Mutation Taster		=91/9	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: rs775931625; hg19: chrX-129546778; COSMIC: COSV100564783; COSMIC: COSV100564783;