Genetic Variant NM_018015.6:c.2411G>A (chrX-106669304-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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. 12/18 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

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2661137.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 17 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018015.6. 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
	RADX	NM_018015.6	MANE Select	c.2411G>A	p.Arg804Gln	missense	Exon 13 of 14	NP_060485.4
	RADX	NM_001184782.2		c.2120G>A	p.Arg707Gln	missense	Exon 12 of 13	NP_001171711.1	Q6NSI4-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RADX	ENST00000372548.9	TSL:1 MANE Select	c.2411G>A	p.Arg804Gln	missense	Exon 13 of 14	ENSP00000361628.4	Q6NSI4-1
RADX	ENST00000372544.6	TSL:2	c.2120G>A	p.Arg707Gln	missense	Exon 12 of 13	ENSP00000361623.2	Q6NSI4-4
RADX	ENST00000421550.1	TSL:2	c.1544G>A	p.Arg515Gln	missense	Exon 12 of 13	ENSP00000405866.1	B1AQ74

Frequencies

GnomAD3 genomes

AF:

0.000542

AC:

AN:

110717

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000510

AC:

AN:

174560

AF XY:

0.000467

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 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

African (AFR)

AF:

0.0000383

AC:

AN:

26083

American (AMR)

AF:

0.00

AC:

AN:

34138

Ashkenazi Jewish (ASJ)

AF:

0.000104

AC:

AN:

19152

East Asian (EAS)

AF:

0.00

AC:

AN:

29971

South Asian (SAS)

AF:

0.00

AC:

AN:

52273

European-Finnish (FIN)

AF:

0.0000742

AC:

AN:

40452

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4101

European-Non Finnish (NFE)

AF:

0.00101

AC:

846

AN:

835591

Other (OTH)

AF:

0.000503

AC:

AN:

45710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

116

145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000542

AC:

AN:

110763

Hom.:

Cov.:

AF XY:

0.000515

AC XY:

AN XY:

33041

show subpopulations

African (AFR)

AF:

0.0000658

AC:

AN:

30408

American (AMR)

AF:

0.00

AC:

AN:

10407

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2634

East Asian (EAS)

AF:

0.00

AC:

AN:

3529

South Asian (SAS)

AF:

0.00

AC:

AN:

2582

European-Finnish (FIN)

AF:

0.000509

AC:

AN:

5890

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00102

AC:

AN:

52910

Other (OTH)

AF:

0.000664

AC:

AN:

1505

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000325

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.087

(source)

DANN

Benign

0.59

FATHMM_MKL

Benign

0.0045

LIST_S2

Benign

0.70

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.1

PhyloP100

-2.0

PROVEAN

Benign

-0.45

REVEL

Benign

0.020

Sift

Benign

0.45

Sift4G

Benign

0.55

Vest4

0.083

MVP

0.22

MPC

0.080

ClinPred

0.020

GERP RS

-0.11

gMVP

0.36

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over