Variant 17-43492703-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_004941.3(DHX8):c.526C>T(p.Arg176Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,578,270 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: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

DHX8
NM_004941.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.750

Variant links:

Genes affected

DHX8 (HGNC:2749): (DEAH-box helicase 8) This gene is a member of the DEAH box polypeptide family. The encoded protein contains the DEAH (Asp-Glu-Ala-His) motif which is characteristic of all DEAH box proteins, and is thought to function as an ATP-dependent RNA helicase that regulates the release of spliced mRNAs from spliceosomes prior to their export from the nucleus. This protein may be required for the replication of human immunodeficiency virus type 1 (HIV-1). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

DHX8 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, DHX8

BP4

Computational evidence support a benign effect (MetaRNN=0.23425984).

BS2

High AC in GnomAdExome at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHX8	NM_004941.3 linkuse as main transcript	c.526C>T	p.Arg176Trp	missense_variant	6/23	ENST00000262415.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHX8	ENST00000262415.8 linkuse as main transcript	c.526C>T	p.Arg176Trp	missense_variant	6/23	1	NM_004941.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151992

Hom.:

Cov.:

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000645

AC:

AN:

248228

Hom.:

AF XY:

0.0000670

AC XY:

AN XY:

134392

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000452

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000287

AC:

AN:

1426160

Hom.:

Cov.:

AF XY:

0.0000183

AC XY:

AN XY:

711532

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000269

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000360

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000577

AC:

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

Feb 28, 2023

The c.526C>T (p.R176W) alteration is located in exon 6 (coding exon 6) of the DHX8 gene. This alteration results from a C to T substitution at nucleotide position 526, causing the arginine (R) at amino acid position 176 to be replaced by a tryptophan (W). 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

0.27

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.23

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.30

T;T

Eigen

Benign

-0.0049

Eigen_PC

Benign

0.021

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

0.96

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.5

D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.012

D;D

Polyphen

0.99

D;D

Vest4

0.54

MVP

0.52

MPC

0.51

ClinPred

0.28

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.077

gMVP

0.41

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