Variant 2-74519062-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_133637.3(DQX1):c.1975G>A(p.Val659Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000348 in 1,438,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

DQX1
NM_133637.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.46

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32013935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DQX1	NM_133637.3 link	c.1975G>A	p.Val659Ile	missense_variant	11/12	ENST00000404568.4	NP_598376.2	Q8TE96-1
DQX1	XM_047443583.1 link	c.1621G>A	p.Val541Ile	missense_variant	10/11		XP_047299539.1
DQX1	XM_011532645.1 link	c.1249G>A	p.Val417Ile	missense_variant	8/9		XP_011530947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DQX1	ENST00000404568.4 link	c.1975G>A	p.Val659Ile	missense_variant	11/12	5	NM_133637.3	ENSP00000384621.3	Q8TE96-1
DQX1	ENST00000393951.6 link	c.1975G>A	p.Val659Ile	missense_variant	11/12	2		ENSP00000377523.2	Q8TE96-1
DQX1	ENST00000418139.5 link	n.*795G>A		non_coding_transcript_exon_variant	8/9	5		ENSP00000389196.1	H7BZE3
DQX1	ENST00000418139.5 link	n.*795G>A		3_prime_UTR_variant	8/9	5		ENSP00000389196.1	H7BZE3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000170

AC:

AN:

235866

Hom.:

AF XY:

0.0000314

AC XY:

AN XY:

127358

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:

0.000146

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000348

AC:

AN:

1438244

Hom.:

Cov.:

AF XY:

0.00000561

AC XY:

AN XY:

713122

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:

0.0000482

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

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

Sep 11, 2024

The c.1975G>A (p.V659I) alteration is located in exon 11 (coding exon 10) of the DQX1 gene. This alteration results from a G to A substitution at nucleotide position 1975, causing the valine (V) at amino acid position 659 to be replaced by an isoleucine (I). 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

0.14

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

T;T

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.77

.;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.64

N;N

REVEL

Benign

0.15

Sift

Benign

0.036

D;D

Sift4G

Benign

0.086

T;T

Polyphen

0.98

D;D

Vest4

0.38

MutPred

0.52

Loss of catalytic residue at V659 (P = 0.0583);Loss of catalytic residue at V659 (P = 0.0583);

MVP

0.36

MPC

0.59

ClinPred

0.88

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.081

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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