5-55262920-C-T

Variant names:

• chr5-55262920-C-T
• NM_019030.4:c.3538G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_019030.4(DHX29):​c.3538G>A​(p.Glu1180Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,076 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: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DHX29 NM_019030.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.45
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.838

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019030.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX29	NM_019030.4	MANE Select	c.3538G>A	p.Glu1180Lys	missense	Exon 24 of 27	NP_061903.2	Q7Z478
	DHX29	NM_001345964.2		c.3385G>A	p.Glu1129Lys	missense	Exon 24 of 27	NP_001332893.1
	DHX29	NM_001345965.2		c.1630G>A	p.Glu544Lys	missense	Exon 24 of 27	NP_001332894.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX29	ENST00000251636.10	TSL:1 MANE Select	c.3538G>A	p.Glu1180Lys	missense	Exon 24 of 27	ENSP00000251636.5	Q7Z478
	DHX29	ENST00000504778.5	TSL:1	n.3746G>A		non_coding_transcript_exon	Exon 24 of 27
	DHX29	ENST00000867273.1		c.3556G>A	p.Glu1186Lys	missense	Exon 24 of 27	ENSP00000537332.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459076 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726014

African (AFR) AF: 0.00 AC: 0 AN: 33370

American (AMR) AF: 0.0000224 AC: 1 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26036

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109886

Other (OTH) AF: 0.00 AC: 0 AN: 60308

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	2.0	M
PhyloP100		7.4
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.010	D
Polyphen		0.97	D
Vest4		0.74
MutPred		0.77		Gain of MoRF binding (P = 0.0121)
MVP		0.60
MPC		0.85
ClinPred		0.94	D
GERP RS		5.3
Varity_R		0.24
gMVP		0.86
Mutation Taster		=44/56	disease causing

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

Other links and lift over

hg19: chr5-54558748;