dbSNP rs769576678: DHX30:p.Pro82Gln (chr3-47827467-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2PM5BP4

The NM_138615.3(DHX30):c.245C>A(p.Pro82Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P82L) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DHX30
NM_138615.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.76

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr3-47827467-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1066052.We mark this variant Likely_pathogenic, oryginal submission is: [Conflicting_classifications_of_pathogenicity].

BP4

Computational evidence support a benign effect (MetaRNN=0.28848472).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHX30	NM_138615.3 link	c.245C>A	p.Pro82Gln	missense_variant	Exon 5 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.245C>A	p.Pro82Gln	missense_variant	Exon 5 of 22	1	NM_138615.3	ENSP00000405620.1		Q7L2E3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457948

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725178

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33214

American (AMR)

AF:

0.00

AC:

AN:

43940

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26018

East Asian (EAS)

AF:

0.00

AC:

AN:

39584

South Asian (SAS)

AF:

0.00

AC:

AN:

85316

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110612

Other (OTH)

AF:

0.00

AC:

AN:

60220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.00083

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

T;T;T;.;.

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

.;D;D;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.29

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.60

N;.;N;.;.

PhyloP100

4.8

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.3

N;N;.;.;N

REVEL

Benign

0.23

Sift

Uncertain

0.0010

D;D;.;.;D

Sift4G

Uncertain

0.0080

D;D;D;D;D

Polyphen

1.0

D;.;D;D;D

Vest4

0.43

MutPred

0.28

Loss of glycosylation at P82 (P = 0.005);.;Loss of glycosylation at P82 (P = 0.005);.;.;

MVP

0.38

MPC

1.8

ClinPred

0.84

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.64

Mutation Taster

=54/46

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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rs769576678

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over