11-110255294-C-T

Position:

• chr11-110255294-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002906.4(RDX):​c.790G>A​(p.Ala264Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000365 in 1,369,408 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000037 (1 hom.)
• Consequence: RDX NM_002906.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.02

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RDX	NM_002906.4	c.790G>A	p.Ala264Thr	missense_variant	8/14	ENST00000645495.2	NP_002897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RDX	ENST00000645495.2	c.790G>A	p.Ala264Thr	missense_variant	8/14		NM_002906.4	ENSP00000496503	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000365 AC: 5 AN: 1369408 Hom.: 1 Cov.: 24 AF XY: 0.00000583 AC XY: 4 AN XY: 686592

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000486

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.89	.;.;.;D;.;D
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.78	.;.;T;.;T;T
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.66	D;D;D;D;D;D
MetaSVM	Uncertain	0.060	D
MutationAssessor	Uncertain	2.1	M;M;M;M;.;M
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.9	D;.;D;D;D;.
REVEL	Uncertain	0.63
Sift	Uncertain	0.0060	D;.;D;D;D;.
Sift4G	Benign	0.061	T;.;T;T;D;.
Polyphen		0.0030	.;.;.;B;.;B
Vest4		0.73
MutPred		0.39		Gain of phosphorylation at A264 (P = 0.0219);Gain of phosphorylation at A264 (P = 0.0219);Gain of phosphorylation at A264 (P = 0.0219);Gain of phosphorylation at A264 (P = 0.0219);.;Gain of phosphorylation at A264 (P = 0.0219);
MVP		0.89
MPC		0.22
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.60
gMVP		0.45

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

Other links and lift over

dbSNP: rs201031650; hg19: chr11-110126019;