Variant 5-55270451-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_019030.4(DHX29):c.3030C>G(p.Ile1010Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,460,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

DHX29
NM_019030.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0330

Variant links:

Genes affected

DHX29 (HGNC:15815): (DExH-box helicase 29) This gene encodes a member of the DEAH (Asp-Glu-Ala-His) subfamily of proteins, part of the DEAD (Asp-Glu-Ala-Asp) box family of RNA helicases. The encoded protein functions in translation initiation, and is specifically required for ribosomal scanning across stable mRNA secondary structures during initiation codon selection. This protein may also play a role in sensing virally derived cytosolic nucleic acids. Knockdown of this gene results in reduced protein translation and impaired proliferation of cancer cells. [provided by RefSeq, Sep 2016]

DHX29 links:

CCNO-DT (HGNC:55543): (CCNO divergent transcript)

CCNO-DT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.844

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHX29	NM_019030.4 linkuse as main transcript	c.3030C>G	p.Ile1010Met	missense_variant	20/27	ENST00000251636.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DHX29	ENST00000251636.10 linkuse as main transcript	c.3030C>G	p.Ile1010Met	missense_variant	20/27	1	NM_019030.4	P1
DHX29	ENST00000504778.5 linkuse as main transcript	n.3238C>G		non_coding_transcript_exon_variant	20/27	1
CCNO-DT	ENST00000506435.1 linkuse as main transcript	n.108-9082G>C		intron_variant, non_coding_transcript_variant		3
DHX29	ENST00000513447.1 linkuse as main transcript	n.837C>G		non_coding_transcript_exon_variant	6/6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249522

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000822

AC:

AN:

1460502

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726530

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

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

Jun 02, 2023

The c.3030C>G (p.I1010M) alteration is located in exon 20 (coding exon 20) of the DHX29 gene. This alteration results from a C to G substitution at nucleotide position 3030, causing the isoleucine (I) at amino acid position 1010 to be replaced by a methionine (M). 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

0.17

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Benign

-0.12

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.021

MetaRNN

Pathogenic

0.84

D;D

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.56

N;.

MutationTaster

Benign

0.51

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.16

N;.

REVEL

Benign

0.28

Sift

Benign

1.0

T;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.54

P;.

Vest4

0.92

MutPred

0.76

Loss of catalytic residue at I1010 (P = 0.0088);Loss of catalytic residue at I1010 (P = 0.0088);

MVP

0.48

MPC

0.61

ClinPred

0.23

GERP RS

-1.9

Varity_R

0.063

gMVP

0.83

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