Variant 5-55261403-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_019030.4(DHX29):c.3925C>T(p.Arg1309Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000165 in 1,579,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

DHX29
NM_019030.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31588966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHX29	NM_019030.4 linkuse as main transcript	c.3925C>T	p.Arg1309Cys	missense_variant	25/27	ENST00000251636.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DHX29	ENST00000251636.10 linkuse as main transcript	c.3925C>T	p.Arg1309Cys	missense_variant	25/27	1	NM_019030.4	P1
DHX29	ENST00000504778.5 linkuse as main transcript	n.4133C>T		non_coding_transcript_exon_variant	25/27	1
CCNO-DT	ENST00000506435.1 linkuse as main transcript	n.108-18130G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151906

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000241

AC:

AN:

248532

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134598

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000596

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000559

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000126

AC:

AN:

1427246

Hom.:

Cov.:

AF XY:

0.0000126

AC XY:

AN XY:

712376

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000688

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000831

Gnomad4 OTH exome

AF:

0.0000677

GnomAD4 genome

AF:

0.0000527

AC:

AN:

151906

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74176

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000624

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

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

Aug 22, 2023

The c.3925C>T (p.R1309C) alteration is located in exon 25 (coding exon 25) of the DHX29 gene. This alteration results from a C to T substitution at nucleotide position 3925, causing the arginine (R) at amino acid position 1309 to be replaced by a cysteine (C). 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

0.18

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.38

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;T

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.8

D;.

REVEL

Benign

0.21

Sift

Benign

0.042

D;.

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

D;.

Vest4

0.41

MVP

0.54

MPC

0.32

ClinPred

0.92

GERP RS

5.9

Varity_R

0.17

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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