Genetic Variant RADX:c.980-8T>C (chrX-106632617-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 (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 id is 2661132.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RADX	NM_018015.6 link	c.980-8T>C	splice_region_variant, intron_variant	Intron 3 of 13	ENST00000372548.9	NP_060485.4	Q6NSI4-1
RADX	NM_001184782.2 link	c.980-8T>C	splice_region_variant, intron_variant	Intron 3 of 12		NP_001171711.1	Q6NSI4-4
RADX	XM_047442233.1 link	c.980-8T>C	splice_region_variant, intron_variant	Intron 3 of 8		XP_047298189.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RADX	ENST00000372548.9 link	c.980-8T>C	splice_region_variant, intron_variant	Intron 3 of 13	1	NM_018015.6	ENSP00000361628.4	Q6NSI4-1
RADX	ENST00000372544.6 link	c.980-8T>C	splice_region_variant, intron_variant	Intron 3 of 12	2		ENSP00000361623.2	Q6NSI4-4
RADX	ENST00000421550.1 link	c.404-8T>C	splice_region_variant, intron_variant	Intron 3 of 12	2		ENSP00000405866.1	B1AQ74
RADX	ENST00000461251.5 link	n.980-8T>C	splice_region_variant, intron_variant	Intron 3 of 8	5		ENSP00000432238.1	Q6NSI4-2

Frequencies

GnomAD3 genomes

AF:

0.000251

AC:

AN:

111506

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33698

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

GnomAD3 exomes

AF:

0.000248

AC:

AN:

165058

Hom.:

AF XY:

0.000203

AC XY:

AN XY:

54302

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 SAS 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

Gnomad4 AFR exome

AF:

0.000206

Gnomad4 AMR exome

AF:

0.000486

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000622

Gnomad4 OTH exome

AF:

0.000372

GnomAD4 genome

AF:

0.000251

AC:

AN:

111554

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33756

show subpopulations

Gnomad4 AFR

AF:

0.0000325

Gnomad4 AMR

AF:

0.000383

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000434

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000347

Hom.:

Bravo

AF:

0.000321

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RADX: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.4

DANN

Benign

0.80

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

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