Genetic Variant RADX:p.Gln610Arg (chrX-106640646-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_018015.6(RADX):c.1829A>G(p.Gln610Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000067 in 1,193,431 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000055 ( 0 hom. 2 hem. )

Consequence

RADX
NM_018015.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.548

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1011875).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RADX	NM_018015.6 link	c.1829A>G	p.Gln610Arg	missense_variant	Exon 10 of 14	ENST00000372548.9	NP_060485.4	Q6NSI4-1
RADX	NM_001184782.2 link	c.1538A>G	p.Gln513Arg	missense_variant	Exon 9 of 13		NP_001171711.1	Q6NSI4-4
RADX	XM_047442233.1 link	c.*87A>G		downstream_gene_variant			XP_047298189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RADX	ENST00000372548.9 link	c.1829A>G	p.Gln610Arg	missense_variant	Exon 10 of 14	1	NM_018015.6	ENSP00000361628.4		Q6NSI4-1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34050

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000112

AC:

AN:

178452

Hom.:

AF XY:

0.0000158

AC XY:

AN XY:

63162

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000248

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000555

AC:

AN:

1081555

Hom.:

Cov.:

AF XY:

0.00000575

AC XY:

AN XY:

347893

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000724

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34050

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 05, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1829A>G (p.Q610R) alteration is located in exon 10 (coding exon 10) of the CXorf57 gene. This alteration results from a A to G substitution at nucleotide position 1829, causing the glutamine (Q) at amino acid position 610 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.97

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.43

T;T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.89

N;N;N

REVEL

Benign

0.020

Sift

Benign

0.27

.;T;D

Sift4G

Benign

0.11

T;D;T

Vest4

0.17

MutPred

0.25

.;Gain of MoRF binding (P = 0.0584);.;

MVP

0.44

MPC

1.1

ClinPred

0.12

GERP RS

1.8

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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