11-110258186-T-C

Variant names:

• chr11-110258186-T-C
• rs376917034
• NM_002906.4:c.471A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_002906.4(RDX):​c.471A>G​(p.Val157Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,581,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V157V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: RDX NM_002906.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.215
• Publications: 0 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 11-110258186-T-C is Benign according to our data. Variant chr11-110258186-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 227900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.215 with no splicing effect.

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.471A>G	p.Val157Val	synonymous	Exon 6 of 14	NP_002897.1	B0YJ88
	RDX	NM_001440509.1		c.471A>G	p.Val157Val	synonymous	Exon 6 of 15	NP_001427438.1
	RDX	NM_001260492.2		c.471A>G	p.Val157Val	synonymous	Exon 6 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.471A>G	p.Val157Val	synonymous	Exon 6 of 14	ENSP00000496503.2	P35241-1
	RDX	ENST00000528498.5	TSL:1	c.471A>G	p.Val157Val	synonymous	Exon 6 of 16	ENSP00000432112.1	P35241-5
	RDX	ENST00000530301.5	TSL:1	c.375A>G	p.Val125Val	synonymous	Exon 5 of 8	ENSP00000436277.1	P35241-3

Frequencies

GnomAD3 genomes AF: 0.000100 AC: 15 AN: 149372 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000987

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: 0.000102

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000247 AC: 59 AN: 238440 AF XY: 0.000225

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: 0.0000485

Gnomad NFE exome AF: 0.000514

Gnomad OTH exome AF: 0.000346

GnomAD4 exome AF: 0.000209 AC: 299 AN: 1432578 Hom.: 0 Cov.: 29 AF XY: 0.000203 AC XY: 145 AN XY: 712964

African (AFR) AF: 0.0000615 AC: 2 AN: 32494

American (AMR) AF: 0.00 AC: 0 AN: 43048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25660

East Asian (EAS) AF: 0.00 AC: 0 AN: 39360

South Asian (SAS) AF: 0.00 AC: 0 AN: 82114

European-Finnish (FIN) AF: 0.000192 AC: 10 AN: 51974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5586

European-Non Finnish (NFE) AF: 0.000251 AC: 274 AN: 1093120

Other (OTH) AF: 0.000220 AC: 13 AN: 59222

GnomAD4 genome AF: 0.000100 AC: 15 AN: 149372 Hom.: 0 Cov.: 32 AF XY: 0.000151 AC XY: 11 AN XY: 72692

African (AFR) AF: 0.0000987 AC: 4 AN: 40514

American (AMR) AF: 0.00 AC: 0 AN: 14986

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.00 AC: 0 AN: 4752

European-Finnish (FIN) AF: 0.000102 AC: 1 AN: 9790

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.000148 AC: 10 AN: 67464

Other (OTH) AF: 0.00 AC: 0 AN: 2052

Alfa AF: 0.0000540 Hom.: 0

Bravo AF: 0.000151

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal recessive nonsyndromic hearing loss 24 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.32
PhyloP100		-0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs376917034; hg19: chr11-110128911;