Genetic Variant NM_002139.4:c.889A>G (chrX-136874429-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002139.4(RBMX):c.889A>G(p.Thr297Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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 (★). Synonymous variant affecting the same amino acid position (i.e. T297T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 26)

Consequence

RBMX
NM_002139.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.72

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

syndromic X-linked intellectual disability Shashi type
Inheritance: Unknown, XL Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

RBMX links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028247893).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002139.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBMX	NM_002139.4	MANE Select	c.889A>G	p.Thr297Ala	missense	Exon 9 of 9	NP_002130.2	P38159-1
RBMX	NM_001164803.2		c.540+657A>G		intron	N/A	NP_001158275.1	P38159-3
RBMX	NR_028476.2		n.872A>G		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBMX	ENST00000320676.11	TSL:1 MANE Select	c.889A>G	p.Thr297Ala	missense	Exon 9 of 9	ENSP00000359645.3	P38159-1
RBMX	ENST00000562646.5	TSL:1	c.*631A>G		3_prime_UTR	Exon 8 of 8	ENSP00000457051.1	H3BT71
RBMX	ENST00000568578.5	TSL:1	n.*1113A>G		non_coding_transcript_exon	Exon 7 of 8	ENSP00000457691.1	H3BR27

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.0042

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.19

M_CAP

Benign

0.012

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.28

PhyloP100

3.7

PrimateAI

Benign

0.44

PROVEAN

Benign

1.8

REVEL

Benign

0.18

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.062

MutPred

0.14

Loss of glycosylation at T297 (P = 0.0014)

MVP

0.59

MPC

1.3

ClinPred

0.18

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.085

gMVP

0.36

Mutation Taster

=77/23

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over