Genetic Variant DHX30:p.His90Gln (chr3-47829038-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138615.3(DHX30):c.270C>A(p.His90Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 27)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DHX30
NM_138615.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0950

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with severe motor impairment and absent language
Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

DHX30 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17138222).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHX30	NM_138615.3 link	c.270C>A	p.His90Gln	missense_variant	Exon 6 of 22	ENST00000445061.6	NP_619520.1	Q7L2E3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHX30	ENST00000445061.6 link	c.270C>A	p.His90Gln	missense_variant	Exon 6 of 22	1	NM_138615.3	ENSP00000405620.1		Q7L2E3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1456944

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724816

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33342

American (AMR)

AF:

0.00

AC:

AN:

44368

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25980

East Asian (EAS)

AF:

0.00

AC:

AN:

39490

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85716

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53158

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108954

Other (OTH)

AF:

0.00

AC:

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Neurodevelopmental disorder with severe motor impairment and absent language

Uncertain:1

Jan 07, 2021

Revvity Omics, Revvity

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.068

T;T;T;.;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.92

.;D;D;D;D

M_CAP

Benign

0.0046

MetaRNN

Benign

0.17

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.0

L;.;L;.;.

PhyloP100

0.095

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.1

N;N;.;.;N

REVEL

Benign

0.086

Sift

Benign

0.30

T;T;.;.;T

Sift4G

Benign

0.33

T;T;T;T;T

Polyphen

0.045

B;.;B;B;B

Vest4

0.39

MutPred

0.33

Gain of MoRF binding (P = 0.1007);.;Gain of MoRF binding (P = 0.1007);.;.;

MVP

0.46

MPC

0.95

ClinPred

0.14

GERP RS

2.5

Varity_R

0.055

gMVP

0.84

Mutation Taster

=62/38

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over