11-110255294-C-A

Variant names:

• chr11-110255294-C-A
• rs201031650
• NM_002906.4:c.790G>T

Variant summary

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

The NM_002906.4(RDX):​c.790G>T​(p.Ala264Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000854 in 1,521,412 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A264P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000088 (0 hom.)
• Consequence: RDX NM_002906.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.02
• Publications: 2 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDX	NM_002906.4	MANE Select	c.790G>T	p.Ala264Ser	missense	Exon 8 of 14	NP_002897.1	B0YJ88
	RDX	NM_001440509.1		c.790G>T	p.Ala264Ser	missense	Exon 8 of 15	NP_001427438.1
	RDX	NM_001260492.2		c.790G>T	p.Ala264Ser	missense	Exon 8 of 16	NP_001247421.1	P35241-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDX	ENST00000645495.2	MANE Select	c.790G>T	p.Ala264Ser	missense	Exon 8 of 14	ENSP00000496503.2	P35241-1
	RDX	ENST00000528498.5	TSL:1	c.790G>T	p.Ala264Ser	missense	Exon 8 of 16	ENSP00000432112.1	P35241-5
	RDX	ENST00000528900.5	TSL:1	c.-82-7461G>T		intron	N/A	ENSP00000433580.1	P35241-2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152004 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 249290 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000876 AC: 12 AN: 1369408 Hom.: 0 Cov.: 24 AF XY: 0.00000874 AC XY: 6 AN XY: 686592

African (AFR) AF: 0.00 AC: 0 AN: 31492

American (AMR) AF: 0.0000225 AC: 1 AN: 44402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25534

East Asian (EAS) AF: 0.00 AC: 0 AN: 39080

South Asian (SAS) AF: 0.00 AC: 0 AN: 84174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4964

European-Non Finnish (NFE) AF: 0.0000107 AC: 11 AN: 1029224

Other (OTH) AF: 0.00 AC: 0 AN: 57248

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152004 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74234

African (AFR) AF: 0.00 AC: 0 AN: 41380

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.85	D
Eigen	Benign	-0.049
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.2	L
PhyloP100		6.0
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.47
Sift	Benign	0.17	T
Sift4G	Benign	0.20	T
Polyphen		0.0	B
Vest4		0.47
MutPred		0.41		Loss of catalytic residue at A264 (P = 0.0258)
MVP		0.91
MPC		0.17
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.45
gMVP		0.37
Mutation Taster		=22/78	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: rs201031650; hg19: chr11-110126019;