Variant chr2-74519984-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_133637.3(DQX1):c.1546C>T(p.Arg516Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,614,176 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 9 hom. )

Consequence

DQX1
NM_133637.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.375

Variant links:

Genes affected

DQX1 (HGNC:20410): (DEAQ-box RNA dependent ATPase 1) Predicted to enable RNA binding activity. Predicted to be involved in DNA duplex unwinding. Predicted to be part of spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

DQX1 links:

DQX1 (HGNC:):

DQX1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007205546).

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DQX1	NM_133637.3 linkuse as main transcript	c.1546C>T	p.Arg516Cys	missense_variant	9/12	ENST00000404568.4	NP_598376.2	Q8TE96-1
DQX1	XM_047443583.1 linkuse as main transcript	c.1192C>T	p.Arg398Cys	missense_variant	8/11		XP_047299539.1
DQX1	XM_011532645.1 linkuse as main transcript	c.820C>T	p.Arg274Cys	missense_variant	6/9		XP_011530947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DQX1	ENST00000404568.4 linkuse as main transcript	c.1546C>T	p.Arg516Cys	missense_variant	9/12	5	NM_133637.3	ENSP00000384621.3		Q8TE96-1

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

206

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00118

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00140

AC:

352

AN:

251442

Hom.:

AF XY:

0.00146

AC XY:

198

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.00744

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00101

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00167

Gnomad OTH exome

AF:

0.00358

GnomAD4 exome

AF:

0.00123

AC:

1798

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

959

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00719

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000904

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.00115

Gnomad4 OTH exome

AF:

0.00204

GnomAD4 genome

AF:

0.00135

AC:

206

AN:

152334

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00118

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00162

Hom.:

Bravo

AF:

0.00171

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.00120

AC:

146

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00289

EpiControl

AF:

0.00279

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 08, 2022

The c.1546C>T (p.R516C) alteration is located in exon 9 (coding exon 8) of the DQX1 gene. This alteration results from a C to T substitution at nucleotide position 1546, causing the arginine (R) at amino acid position 516 to be replaced by a cysteine (C). 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

0.22

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;T

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.82

.;T

M_CAP

Benign

0.0088

MetaRNN

Benign

0.0072

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.2

L;L

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.6

D;D

REVEL

Benign

0.20

Sift

Benign

0.030

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.25

B;B

Vest4

0.32

MVP

0.49

MPC

0.26

ClinPred

0.022

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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