NM_002906.4:c.97-10_97-8delTGT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_002906.4(RDX):​c.97-10_97-8delTGT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000513 in 1,611,124 control chromosomes in the GnomAD database, including 11 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00051 ( 11 hom. )

Consequence

RDX
NM_002906.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.33
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 11-110264881-CACA-C is Benign according to our data. Variant chr11-110264881-CACA-C is described in ClinVar as [Likely_benign]. Clinvar id is 179830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000572 (87/152146) while in subpopulation SAS AF= 0.00374 (18/4814). AF 95% confidence interval is 0.00242. There are 0 homozygotes in gnomad4. There are 56 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RDXNM_002906.4 linkc.97-10_97-8delTGT splice_region_variant, intron_variant Intron 3 of 13 ENST00000645495.2 NP_002897.1 P35241-1B0YJ88Q6PKD3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RDXENST00000645495.2 linkc.97-10_97-8delTGT splice_region_variant, intron_variant Intron 3 of 13 NM_002906.4 ENSP00000496503.2 P35241-1

Frequencies

GnomAD3 genomes
AF:
0.000566
AC:
86
AN:
152028
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000893
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.000577
Gnomad EAS
AF:
0.000771
Gnomad SAS
AF:
0.00374
Gnomad FIN
AF:
0.000663
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000857
AC:
215
AN:
250794
Hom.:
1
AF XY:
0.000981
AC XY:
133
AN XY:
135572
show subpopulations
Gnomad AFR exome
AF:
0.000924
Gnomad AMR exome
AF:
0.000318
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000218
Gnomad SAS exome
AF:
0.00416
Gnomad FIN exome
AF:
0.00140
Gnomad NFE exome
AF:
0.000238
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000507
AC:
740
AN:
1458978
Hom.:
11
AF XY:
0.000625
AC XY:
454
AN XY:
726002
show subpopulations
Gnomad4 AFR exome
AF:
0.00141
Gnomad4 AMR exome
AF:
0.000291
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.00420
Gnomad4 FIN exome
AF:
0.00160
Gnomad4 NFE exome
AF:
0.000153
Gnomad4 OTH exome
AF:
0.000414
GnomAD4 genome
AF:
0.000572
AC:
87
AN:
152146
Hom.:
0
Cov.:
32
AF XY:
0.000753
AC XY:
56
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.000915
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.000577
Gnomad4 EAS
AF:
0.000772
Gnomad4 SAS
AF:
0.00374
Gnomad4 FIN
AF:
0.000663
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.000947
Bravo
AF:
0.000438
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000593

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Dec 20, 2022
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Oct 03, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:1
Jun 23, 2016
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

c.97-19TGT[3] in intron 3 of RDX: This variant is not expected to have clinical significance because it has been identified in 0.35% (57/16200) of South Asian c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org). -

RDX-related disorder Benign:1
Jan 21, 2020
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs532650829; hg19: chr11-110135606; API