chr3-47841027-A-G

Position:

chr3-47841027-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2

The NM_138615.3(DHX30):c.517A>G(p.Ile173Val) variant causes a missense change. The variant allele was found at a frequency of 0.000393 in 1,614,188 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00021 ( 2 hom. )

Consequence

DHX30
NM_138615.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.55

Variant links:

Genes affected

DHX30 (HGNC:16716): (DExH-box helicase 30) 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. The family member encoded by this gene is a mitochondrial nucleoid protein that associates with mitochondrial DNA. It has also been identified as a component of a transcriptional repressor complex that functions in retinal development, and it is required to optimize the function of the zinc-finger antiviral protein. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]

DHX30 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DHX30. . Gene score misZ 5.2961 (greater than the threshold 3.09). Trascript score misZ 6.8999 (greater than threshold 3.09). GenCC has associacion of gene with neurodevelopmental disorder with severe motor impairment and absent language.

BP4

Computational evidence support a benign effect (MetaRNN=0.007045299).

BP6

Variant 3-47841027-A-G is Benign according to our data. Variant chr3-47841027-A-G is described in ClinVar as [Benign]. Clinvar id is 3038743.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00217 (330/152312) while in subpopulation AFR AF= 0.0077 (320/41584). AF 95% confidence interval is 0.007. There are 0 homozygotes in gnomad4. There are 152 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 330 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHX30	NM_138615.3 linkuse as main transcript	c.517A>G	p.Ile173Val	missense_variant	7/22	ENST00000445061.6	NP_619520.1	Q7L2E3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHX30	ENST00000445061.6 linkuse as main transcript	c.517A>G	p.Ile173Val	missense_variant	7/22	1	NM_138615.3	ENSP00000405620.1		Q7L2E3-1

Frequencies

GnomAD3 genomes

AF:

0.00217

AC:

330

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000565

AC:

142

AN:

251298

Hom.:

AF XY:

0.000368

AC XY:

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00770

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000209

AC:

305

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

126

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00762

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.00217

AC:

330

AN:

152312

Hom.:

Cov.:

AF XY:

0.00204

AC XY:

152

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00770

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000610

Hom.:

Bravo

AF:

0.00234

ESP6500AA

AF:

0.00794

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000774

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DHX30-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 01, 2019

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

0.062

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

T;T;T;.;.

Eigen

Benign

0.066

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

.;D;D;D;D

M_CAP

Benign

0.0028

MetaRNN

Benign

0.0070

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;.;N;.;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.17

N;N;.;.;N

REVEL

Benign

0.11

Sift

Pathogenic

0.0

D;D;.;.;D

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

0.27

B;.;B;B;B

Vest4

0.38

MVP

0.33

MPC

0.81

ClinPred

0.077

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.078

gMVP

0.36

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