Variant X-106669304-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018015.6(RADX):c.2411G>A(p.Arg804Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00078 in 1,198,234 control chromosomes in the GnomAD database, including 1 homozygotes. There are 289 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., 17 hem., cov: 23)

Exomes 𝑓: 0.00080 ( 1 hom. 272 hem. )

Consequence

RADX
NM_018015.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.05

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=0.016886234).

BP6

Variant X-106669304-G-A is Benign according to our data. Variant chrX-106669304-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2661137.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RADX	NM_018015.6 linkuse as main transcript	c.2411G>A	p.Arg804Gln	missense_variant	13/14	ENST00000372548.9	NP_060485.4	Q6NSI4-1
RADX	NM_001184782.2 linkuse as main transcript	c.2120G>A	p.Arg707Gln	missense_variant	12/13		NP_001171711.1	Q6NSI4-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RADX	ENST00000372548.9 linkuse as main transcript	c.2411G>A	p.Arg804Gln	missense_variant	13/14	1	NM_018015.6	ENSP00000361628.4	Q6NSI4-1
RADX	ENST00000372544.6 linkuse as main transcript	c.2120G>A	p.Arg707Gln	missense_variant	12/13	2		ENSP00000361623.2	Q6NSI4-4
RADX	ENST00000421550.1 linkuse as main transcript	c.1544G>A	p.Arg515Gln	missense_variant	12/13	2		ENSP00000405866.1	B1AQ74

Frequencies

GnomAD3 genomes

AF:

0.000542

AC:

AN:

110717

Hom.:

Cov.:

AF XY:

0.000515

AC XY:

AN XY:

32985

show subpopulations

Gnomad AFR

AF:

0.0000659

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:

0.000509

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00102

Gnomad OTH

AF:

0.000672

GnomAD3 exomes

AF:

0.000510

AC:

AN:

174560

Hom.:

AF XY:

0.000467

AC XY:

AN XY:

59976

show subpopulations

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 SAS exome

AF:

0.0000584

Gnomad FIN exome

AF:

0.0000632

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000805

AC:

875

AN:

1087471

Hom.:

Cov.:

AF XY:

0.000769

AC XY:

272

AN XY:

353601

show subpopulations

Gnomad4 AFR exome

AF:

0.0000383

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000104

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000742

Gnomad4 NFE exome

AF:

0.00101

Gnomad4 OTH exome

AF:

0.000503

GnomAD4 genome

AF:

0.000542

AC:

AN:

110763

Hom.:

Cov.:

AF XY:

0.000515

AC XY:

AN XY:

33041

show subpopulations

Gnomad4 AFR

AF:

0.0000658

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000509

Gnomad4 NFE

AF:

0.00102

Gnomad4 OTH

AF:

0.000664

Alfa

AF:

0.000325

Hom.:

Bravo

AF:

0.000518

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00104

AC:

ExAC

AF:

0.000560

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

RADX: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.087

DANN

Benign

0.59

FATHMM_MKL

Benign

0.0045

LIST_S2

Benign

0.70

T;T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-1.1

PROVEAN

Benign

-0.45

N;N;N

REVEL

Benign

0.020

Sift

Benign

0.45

.;T;T

Sift4G

Benign

0.55

T;T;T

Vest4

0.083

MVP

0.22

MPC

0.080

ClinPred

0.020

GERP RS

-0.11

gMVP

0.36

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