Genetic Variant NM_018015.6:c.980-8T>C (chrX-106632617-T-C) – 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.980-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 1,121,591 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 157 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.00051 ( 0 hom. 153 hem. )

Consequence

RADX
NM_018015.6 splice_region, intron

Scores

Splicing: ADA: 0.00007433

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.428

Publications

0 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 (BayesDel_noAF=-0.55).

BP6

Variant X-106632617-T-C is Benign according to our data. Variant chrX-106632617-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2661132.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 4 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.980-8T>C		splice_region intron	N/A	NP_060485.4
	RADX	NM_001184782.2		c.980-8T>C		splice_region intron	N/A	NP_001171711.1	Q6NSI4-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RADX	ENST00000372548.9	TSL:1 MANE Select	c.980-8T>C	splice_region intron	N/A	ENSP00000361628.4	Q6NSI4-1
RADX	ENST00000372544.6	TSL:2	c.980-8T>C	splice_region intron	N/A	ENSP00000361623.2	Q6NSI4-4
RADX	ENST00000421550.1	TSL:2	c.404-8T>C	splice_region intron	N/A	ENSP00000405866.1	B1AQ74

Frequencies

GnomAD3 genomes

AF:

0.000251

AC:

AN:

111506

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000384

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:

0.000434

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000248

AC:

AN:

165058

AF XY:

0.000203

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000453

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000334

Gnomad OTH exome

AF:

0.00124

GnomAD4 exome

AF:

0.000510

AC:

515

AN:

1010037

Hom.:

Cov.:

AF XY:

0.000508

AC XY:

153

AN XY:

301447

show subpopulations

African (AFR)

AF:

0.000206

AC:

AN:

24217

American (AMR)

AF:

0.000486

AC:

AN:

32897

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18400

East Asian (EAS)

AF:

0.00

AC:

AN:

29696

South Asian (SAS)

AF:

0.00

AC:

AN:

49486

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40096

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3683

European-Non Finnish (NFE)

AF:

0.000622

AC:

478

AN:

768575

Other (OTH)

AF:

0.000372

AC:

AN:

42987

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

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000251

AC:

AN:

111554

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33756

show subpopulations

African (AFR)

AF:

0.0000325

AC:

AN:

30782

American (AMR)

AF:

0.000383

AC:

AN:

10438

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2638

East Asian (EAS)

AF:

0.00

AC:

AN:

3575

South Asian (SAS)

AF:

0.00

AC:

AN:

2662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5983

Middle Eastern (MID)

AF:

0.00

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.000434

AC:

AN:

53044

Other (OTH)

AF:

0.00

AC:

AN:

1532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

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:

0.000347

Hom.:

Bravo

AF:

0.000321

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

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.4

(source)

DANN

Benign

0.80

PhyloP100

-0.43

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000074

dbscSNV1_RF

Benign

0.0060

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