Genetic Variant RBMX:p.Thr297Thr (chrX-136874427-T-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_002139.4(RBMX):c.891A>G(p.Thr297Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., 0 hem., cov: 26)

Exomes 𝑓: 0.0014 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

RBMX
NM_002139.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.21

Variant links:

Genes affected

RBMX (HGNC:9910): (RNA binding motif protein X-linked) This gene belongs to the RBMY gene family which includes candidate Y chromosome spermatogenesis genes. This gene, an active X chromosome homolog of the Y chromosome RBMY gene, is widely expressed whereas the RBMY gene evolved a male-specific function in spermatogenesis. Pseudogenes of this gene, found on chromosomes 1, 4, 9, 11, and 6, were likely derived by retrotransposition from the original gene. Alternatively spliced transcript variants encoding different isoforms have been identified. A snoRNA gene (SNORD61) is found in one of its introns. [provided by RefSeq, Sep 2009]

RBMX links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant X-136874427-T-C is Benign according to our data. Variant chrX-136874427-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 403368.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.21 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBMX	NM_002139.4 link	c.891A>G	p.Thr297Thr	synonymous_variant	Exon 9 of 9	ENST00000320676.11	NP_002130.2	P38159-1
RBMX	NM_001164803.2 link	c.540+659A>G		intron_variant	Intron 6 of 7		NP_001158275.1	P38159-3
RBMX	NR_028476.2 link	n.874A>G		non_coding_transcript_exon_variant	Exon 8 of 8
RBMX	NR_028477.2 link	n.1081A>G		non_coding_transcript_exon_variant	Exon 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMX	ENST00000320676.11 link	c.891A>G	p.Thr297Thr	synonymous_variant	Exon 9 of 9	1	NM_002139.4	ENSP00000359645.3		P38159-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

156

AN:

93779

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

26699

FAILED QC

Gnomad AFR

AF:

0.00158

Gnomad AMI

AF:

0.00828

Gnomad AMR

AF:

0.00187

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00121

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00196

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.000136

AC:

AN:

161359

Hom.:

AF XY:

0.00

AC XY:

AN XY:

54747

show subpopulations

Gnomad AFR exome

AF:

0.0000856

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000312

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000264

Gnomad OTH exome

AF:

0.000257

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00137

AC:

1276

AN:

928774

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

270166

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00185

Gnomad4 ASJ exome

AF:

0.00382

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000265

Gnomad4 FIN exome

AF:

0.00240

Gnomad4 NFE exome

AF:

0.00139

Gnomad4 OTH exome

AF:

0.00148

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00166

AC:

156

AN:

93825

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

26757

show subpopulations

Gnomad4 AFR

AF:

0.00158

Gnomad4 AMR

AF:

0.00187

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00121

Gnomad4 NFE

AF:

0.00196

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.0378

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Silent variant not near splice site -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over