Genetic Variant RDX:c.1091-10T>C (chr11-110237662-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_002906.4(RDX):c.1091-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The gene RDX is a tumor suppressor gene (CancerMine: 2 TSG citations). The variant allele was found at a cumulative frequency of 0.00000137 (AC=2) in the gnomAD database across 1,461,300 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.0000003. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Variant has been reported in ClinVar as Benign/Likely Benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RDX
NM_002906.4 intron

Scores

Splicing: ADA: 0.003096

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.29

Publications

0 publications found

Variant links:

Genes affected

RDX (HGNC:9944): (radixin) Radixin is a cytoskeletal protein that may be important in linking actin to the plasma membrane. It is highly similar in sequence to both ezrin and moesin. The radixin gene has been localized by fluorescence in situ hybridization to 11q23. A truncated version representing a pseudogene (RDXP2) was assigned to Xp21.3. Another pseudogene that seemed to lack introns (RDXP1) was mapped to 11p by Southern and PCR analyses. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

RDX Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive nonsyndromic hearing loss 24
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

RDX links:

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new If you want to explore the variant's impact on the transcript NM_002906.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 points.

Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = 0.000000, AC = 2 — absent/extremely rare (O3 moderate [+2])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_002906.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RDX	NM_002906.4	MANE Select	c.1091-10T>C	intron	N/A	NP_002897.1	B0YJ88
RDX	NM_001440509.1		c.1277-10T>C	intron	N/A	NP_001427438.1
RDX	NM_001260492.2		c.1091-10T>C	intron	N/A	NP_001247421.1	P35241-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RDX	ENST00000645495.2	MANE Select	c.1091-10T>C	intron	N/A	ENSP00000496503.2	P35241-1
RDX	ENST00000528498.5	TSL:1	c.1091-10T>C	intron	N/A	ENSP00000432112.1	P35241-5
RDX	ENST00000528900.5	TSL:1	c.50-10T>C	intron	N/A	ENSP00000433580.1	P35241-2

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes					32
GnomAD4 exome	0.00000137	2	0	1461300	30
GnomAD4 genome					32

Showing 3 sources

Case/control cohorts

Cohort	Cases			Controls
Cohort	AF	AC	AN	AF	AC	AN
BipEx (Bipolar disorder (including schizoaffective))	0.0000352	1	28420	0.00	0	28844

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Benign	-	8.8
BayesDel_noAF	Benign	-	-0.75
BranchPoint Hunter	N/A	-	4.0
CADD	Benign	-	1.5
DANN	Benign	-	0.59
GPN-Star LLR	N/A	-	-2.5
GPN-Star score	N/A	-	2.5
PhyloP100	Benign	-	3.3

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated prediction	Prediction	Score
dbscSNV1_ADA	Benign	-	0.0031
dbscSNV1_RF	Benign	-	0.080
DS_AL_spliceai	Uncertain	- Position offset: -10	0.22
Pangolin (max)	Benign	-	0.090
SpliceAI score (max)	Uncertain	- Details are displayed if max score is > 0.2	0.22

Showing 5 of 5 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Case/control cohorts

ClinVar

Computational Scores

Splicing Scores

Publications

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