X-130402255-C-T

Variant names:

• chrX-130402255-C-T
• rs768008291
• NM_016024.4:c.6C>T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

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: Splicing: ADA: 0.001205
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.16

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

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
RBMX2	NM_016024.4	c.6C>T	p.Asn2Asn	splice_region_variant, synonymous_variant	Exon 2 of 6	ENST00000305536.11	NP_057108.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMX2	ENST00000305536.11	c.6C>T	p.Asn2Asn	splice_region_variant, synonymous_variant	Exon 2 of 6	1	NM_016024.4	ENSP00000339090.4
RBMX2	ENST00000469953.1	n.255C>T		non_coding_transcript_exon_variant	Exon 1 of 4	1
RBMX2	ENST00000370947.1	c.6C>T	p.Asn2Asn	splice_region_variant, synonymous_variant	Exon 2 of 3	2		ENSP00000359985.1

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

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

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

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

Other links and lift over

dbSNP: rs768008291; hg19: chrX-129536229;