Variant 19-47353079-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_014681.6(DHX34):c.49C>T(p.Arg17Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 1,614,032 control chromosomes in the GnomAD database, including 3,216 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.046 ( 225 hom., cov: 32)

Exomes 𝑓: 0.059 ( 2991 hom. )

Consequence

DHX34
NM_014681.6 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.05

Variant links:

Genes affected

DHX34 (HGNC:16719): (DExH-box helicase 34) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a member of this family. It is mapped to the glioma 19q tumor suppressor region and is a tumor suppressor candidate gene. [provided by RefSeq, Jul 2008]

DHX34 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020906627).

BP6

Variant 19-47353079-C-T is Benign according to our data. Variant chr19-47353079-C-T is described in ClinVar as [Benign]. Clinvar id is 3056984.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHX34	NM_014681.6 linkuse as main transcript	c.49C>T	p.Arg17Trp	missense_variant	2/17	ENST00000328771.9	NP_055496.2	Q14147

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHX34	ENST00000328771.9 linkuse as main transcript	c.49C>T	p.Arg17Trp	missense_variant	2/17	5	NM_014681.6	ENSP00000331907.4		Q14147

Frequencies

GnomAD3 genomes

AF:

0.0459

AC:

6984

AN:

152154

Hom.:

225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0121

Gnomad AMI

AF:

0.0614

Gnomad AMR

AF:

0.0441

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0625

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0689

Gnomad OTH

AF:

0.0516

GnomAD3 exomes

AF:

0.0472

AC:

11860

AN:

251054

Hom.:

350

AF XY:

0.0478

AC XY:

6496

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.00933

Gnomad AMR exome

AF:

0.0329

Gnomad ASJ exome

AF:

0.0650

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0139

Gnomad FIN exome

AF:

0.0628

Gnomad NFE exome

AF:

0.0687

Gnomad OTH exome

AF:

0.0550

GnomAD4 exome

AF:

0.0591

AC:

86413

AN:

1461760

Hom.:

2991

Cov.:

AF XY:

0.0583

AC XY:

42391

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.00947

Gnomad4 AMR exome

AF:

0.0334

Gnomad4 ASJ exome

AF:

0.0661

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0139

Gnomad4 FIN exome

AF:

0.0626

Gnomad4 NFE exome

AF:

0.0673

Gnomad4 OTH exome

AF:

0.0532

GnomAD4 genome

AF:

0.0459

AC:

6984

AN:

152272

Hom.:

225

Cov.:

AF XY:

0.0443

AC XY:

3296

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0120

Gnomad4 AMR

AF:

0.0440

Gnomad4 ASJ

AF:

0.0657

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0124

Gnomad4 FIN

AF:

0.0625

Gnomad4 NFE

AF:

0.0689

Gnomad4 OTH

AF:

0.0511

Alfa

AF:

0.0639

Hom.:

829

Bravo

AF:

0.0433

TwinsUK

AF:

0.0623

AC:

231

ALSPAC

AF:

0.0573

AC:

221

ESP6500AA

AF:

0.0129

AC:

ESP6500EA

AF:

0.0672

AC:

578

ExAC

AF:

0.0474

AC:

5755

Asia WGS

AF:

0.00924

AC:

AN:

3478

EpiCase

AF:

0.0695

EpiControl

AF:

0.0705

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DHX34-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 04, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.019

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.68

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.84

REVEL

Benign

0.0080

Sift

Benign

0.14

Sift4G

Benign

0.072

Polyphen

0.0010

Vest4

0.063

MPC

0.19

ClinPred

0.0068

GERP RS

-0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.037

gMVP

0.33

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

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