chrX-130409342-C-A

Variant names:

• chrX-130409342-C-A
• rs201100723
• NM_016024.4:c.259C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016024.4(RBMX2):​c.259C>A​(p.Gln87Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000995 in 1,206,482 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000037 (0 hom. 0 hem.)
• Consequence: RBMX2 NM_016024.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.27
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25762284).

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.259C>A	p.Gln87Lys	missense	Exon 4 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.259C>A	p.Gln87Lys	missense	Exon 4 of 6	ENSP00000339090.4	Q9Y388
	RBMX2	ENST00000469953.1	TSL:1	n.508C>A		non_coding_transcript_exon	Exon 3 of 4
	RBMX2	ENST00000919759.1		c.256C>A	p.Gln86Lys	missense	Exon 4 of 6	ENSP00000589818.1

Frequencies

GnomAD3 genomes AF: 0.0000718 AC: 8 AN: 111448 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000954

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000111 AC: 2 AN: 179676 AF XY: 0.00

Gnomad AFR exome AF: 0.0000814

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: 0.00

Gnomad OTH exome AF: 0.000228

GnomAD4 exome AF: 0.00000365 AC: 4 AN: 1094982 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 360478

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

African (AFR) AF: 0.000152 AC: 4 AN: 26338

American (AMR) AF: 0.00 AC: 0 AN: 35033

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19328

East Asian (EAS) AF: 0.00 AC: 0 AN: 30131

South Asian (SAS) AF: 0.00 AC: 0 AN: 53479

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4123

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840116

Other (OTH) AF: 0.00 AC: 0 AN: 45972

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000286219), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000717 AC: 8 AN: 111500 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33682

African (AFR) AF: 0.000228 AC: 7 AN: 30682

American (AMR) AF: 0.0000953 AC: 1 AN: 10496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3575

South Asian (SAS) AF: 0.00 AC: 0 AN: 2608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5969

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53122

Other (OTH) AF: 0.00 AC: 0 AN: 1509

Alfa AF: 0.000214 Hom.: 1

Bravo AF: 0.0000793

ESP6500AA AF: 0.000320 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

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	Pathogenic	0.93
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.32	N
PhyloP100		7.3
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.38	B
Vest4		0.73
MVP		0.79
MPC		1.3
ClinPred		0.47	T
GERP RS		5.5
Varity_R		0.95
gMVP		0.82
Mutation Taster		=27/73	disease causing

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: rs201100723; hg19: chrX-129543316;