Variant X-106612538-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000372548.9(RADX):c.458T>C(p.Val153Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00051 in 1,209,452 control chromosomes in the GnomAD database, including 2 homozygotes. There are 175 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 0 hom., 88 hem., cov: 23)

Exomes 𝑓: 0.00028 ( 2 hom. 87 hem. )

Consequence

RADX
ENST00000372548.9 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.73

Variant links:

Genes affected

RADX (HGNC:25486): (RPA1 related single stranded DNA binding protein, X-linked) Enables single-stranded DNA binding activity. Involved in negative regulation of double-strand break repair via homologous recombination. Located in nuclear speck and replication fork. [provided by Alliance of Genome Resources, Apr 2022]

RADX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006502211).

BP6

Variant X-106612538-T-C is Benign according to our data. Variant chrX-106612538-T-C is described in ClinVar as [Benign]. Clinvar id is 727511.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 88 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RADX	NM_018015.6 linkuse as main transcript	c.458T>C	p.Val153Ala	missense_variant	1/14	ENST00000372548.9	NP_060485.4
RADX	NM_001184782.2 linkuse as main transcript	c.458T>C	p.Val153Ala	missense_variant	1/13		NP_001171711.1
RADX	XM_047442233.1 linkuse as main transcript	c.458T>C	p.Val153Ala	missense_variant	1/9		XP_047298189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RADX	ENST00000372548.9 linkuse as main transcript	c.458T>C	p.Val153Ala	missense_variant	1/14	1	NM_018015.6	ENSP00000361628	P1	Q6NSI4-1
RADX	ENST00000372544.6 linkuse as main transcript	c.458T>C	p.Val153Ala	missense_variant	1/13	2		ENSP00000361623		Q6NSI4-4
RADX	ENST00000461251.5 linkuse as main transcript	c.458T>C	p.Val153Ala	missense_variant, NMD_transcript_variant	1/9	5		ENSP00000432238		Q6NSI4-2

Frequencies

GnomAD3 genomes

AF:

0.00275

AC:

307

AN:

111566

Hom.:

Cov.:

AF XY:

0.00261

AC XY:

AN XY:

33760

show subpopulations

Gnomad AFR

AF:

0.00963

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000760

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:

0.00

Gnomad OTH

AF:

0.00267

GnomAD3 exomes

AF:

0.000715

AC:

131

AN:

183334

Hom.:

AF XY:

0.000368

AC XY:

AN XY:

67852

show subpopulations

Gnomad AFR exome

AF:

0.00945

Gnomad AMR exome

AF:

0.000182

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000442

GnomAD4 exome

AF:

0.000281

AC:

309

AN:

1097835

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

AN XY:

363193

show subpopulations

Gnomad4 AFR exome

AF:

0.0100

Gnomad4 AMR exome

AF:

0.000341

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000594

Gnomad4 OTH exome

AF:

0.000586

GnomAD4 genome

AF:

0.00276

AC:

308

AN:

111617

Hom.:

Cov.:

AF XY:

0.00260

AC XY:

AN XY:

33821

show subpopulations

Gnomad4 AFR

AF:

0.00964

Gnomad4 AMR

AF:

0.000760

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00264

Alfa

AF:

0.000232

Hom.:

Bravo

AF:

0.00329

ESP6500AA

AF:

0.00756

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000717

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.65

T;T

MetaRNN

Benign

0.0065

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.98

N;N

PROVEAN

Benign

-0.96

N;N

REVEL

Benign

0.11

Sift

Uncertain

0.0070

.;D

Sift4G

Uncertain

0.044

D;D

Vest4

0.39

MVP

0.49

MPC

1.4

ClinPred

0.044

GERP RS

2.8

gMVP

0.73

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over