Variant 2-74518483-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_133637.3(DQX1):c.2117C>T(p.Ser706Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

DQX1
NM_133637.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.91

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10307783).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DQX1	NM_133637.3 linkuse as main transcript	c.2117C>T	p.Ser706Leu	missense_variant	12/12	ENST00000404568.4	NP_598376.2	Q8TE96-1
DQX1	XM_047443583.1 linkuse as main transcript	c.1763C>T	p.Ser588Leu	missense_variant	11/11		XP_047299539.1
DQX1	XM_011532645.1 linkuse as main transcript	c.1391C>T	p.Ser464Leu	missense_variant	9/9		XP_011530947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DQX1	ENST00000404568.4 linkuse as main transcript	c.2117C>T	p.Ser706Leu	missense_variant	12/12	5	NM_133637.3	ENSP00000384621.3	Q8TE96-1
DQX1	ENST00000393951.6 linkuse as main transcript	c.2117C>T	p.Ser706Leu	missense_variant	12/12	2		ENSP00000377523.2	Q8TE96-1
DQX1	ENST00000418139.5 linkuse as main transcript	n.*937C>T		non_coding_transcript_exon_variant	9/9	5		ENSP00000389196.1	H7BZE3
DQX1	ENST00000418139.5 linkuse as main transcript	n.*937C>T		3_prime_UTR_variant	9/9	5		ENSP00000389196.1	H7BZE3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727244

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:

0.0000189

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Oct 26, 2024

The c.2117C>T (p.S706L) alteration is located in exon 12 (coding exon 11) of the DQX1 gene. This alteration results from a C to T substitution at nucleotide position 2117, causing the serine (S) at amino acid position 706 to be replaced by a leucine (L). 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

0.075

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0066

T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.66

.;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.58

N;N

REVEL

Benign

0.030

Sift

Benign

0.061

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.28

B;B

Vest4

0.23

MutPred

0.18

Loss of phosphorylation at S706 (P = 0.0185);Loss of phosphorylation at S706 (P = 0.0185);

MVP

0.21

MPC

0.20

ClinPred

0.64

GERP RS

4.3

Varity_R

0.066

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over