chr11-110237567-C-G

Variant names:

• chr11-110237567-C-G
• rs727505297
• NM_002906.4:c.1176G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002906.4(RDX):​c.1176G>C​(p.Glu392Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E392K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RDX NM_002906.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.282
• Publications: 1 publications found

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: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15463552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RDX	NM_002906.4	c.1176G>C	p.Glu392Asp	missense_variant	Exon 11 of 14	ENST00000645495.2	NP_002897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RDX	ENST00000645495.2	c.1176G>C	p.Glu392Asp	missense_variant	Exon 11 of 14		NM_002906.4	ENSP00000496503.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	.;.;.;.;D;.;D
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.86	.;.;D;D;.;D;D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.15	T;T;T;T;T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.7	L;L;L;.;L;.;L
PhyloP100		-0.28
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.9	N;.;N;N;N;N;.
REVEL	Benign	0.24
Sift	Benign	0.15	T;.;T;T;T;T;.
Sift4G	Benign	0.14	T;.;T;T;T;T;.
Polyphen		0.10	.;.;.;.;B;.;B
Vest4		0.28
MutPred		0.55		Gain of MoRF binding (P = 0.0584);Gain of MoRF binding (P = 0.0584);Gain of MoRF binding (P = 0.0584);.;Gain of MoRF binding (P = 0.0584);.;Gain of MoRF binding (P = 0.0584);
MVP		0.64
MPC		0.15
ClinPred		0.37	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.077
gMVP		0.83
Mutation Taster		=33/67	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: rs727505297; hg19: chr11-110108292;