Genetic Variant RDX:c.*388C>T (chr11-110195809-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001260492.2(RDX):c.*388C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,962 control chromosomes in the GnomAD database, including 11,648 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.39 ( 11648 hom., cov: 32)

Exomes 𝑓: 0.083 ( 0 hom. )

Consequence

RDX
NM_001260492.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.489

Publications

2 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), Ambry Genetics
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

RDX links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001260492.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
RDX	NM_001260492.2	c.*388C>T	3_prime_UTR	Exon 16 of 16	NP_001247421.1	P35241-5
RDX	NM_001440511.1	c.*388C>T	3_prime_UTR	Exon 15 of 15	NP_001427440.1
RDX	NM_001260495.2	c.*388C>T	3_prime_UTR	Exon 9 of 9	NP_001247424.1	P35241-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RDX	ENST00000528900.5	TSL:1	c.*388C>T	3_prime_UTR	Exon 9 of 9	ENSP00000433580.1	P35241-2
RDX	ENST00000530301.5	TSL:1	c.*388C>T	3_prime_UTR	Exon 8 of 8	ENSP00000436277.1	P35241-3
RDX	ENST00000528498.5	TSL:1	c.*31+3772C>T	intron	N/A	ENSP00000432112.1	P35241-5

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

58846

AN:

151830

Hom.:

11642

Cov.:

show subpopulations

Gnomad AFR

AF:

0.323

Gnomad AMI

AF:

0.499

Gnomad AMR

AF:

0.364

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.603

Gnomad SAS

AF:

0.399

Gnomad FIN

AF:

0.446

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.362

GnomAD4 exome

AF:

0.0833

AC:

AN:

Hom.:

Cov.:

AF XY:

0.125

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.100

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.825

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.388

AC:

58892

AN:

151950

Hom.:

11648

Cov.:

AF XY:

0.388

AC XY:

28833

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.324

AC:

13406

AN:

41422

American (AMR)

AF:

0.364

AC:

5563

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1200

AN:

3470

East Asian (EAS)

AF:

0.602

AC:

3115

AN:

5176

South Asian (SAS)

AF:

0.399

AC:

1922

AN:

4820

European-Finnish (FIN)

AF:

0.446

AC:

4696

AN:

10526

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.407

AC:

27690

AN:

67960

Other (OTH)

AF:

0.365

AC:

769

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1845

3690

5534

7379

9224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

582

1164

1746

2328

2910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.394

Hom.:

1483

Bravo

AF:

0.379

Asia WGS

AF:

0.468

AC:

1631

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.4

(source)

DANN

Benign

0.67

PhyloP100

-0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over