5-55261472-C-G

Variant names:

• chr5-55261472-C-G
• NM_019030.4:c.3856G>C
• DHX29 p.Glu1286Gln

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_019030.4(DHX29):​c.3856G>C​(p.Glu1286Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DHX29 NM_019030.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.05
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.3856G>C	p.Glu1286Gln	missense	Exon 25 of 27	NP_061903.2	Q7Z478
	DHX29	NM_001345964.2		c.3703G>C	p.Glu1235Gln	missense	Exon 25 of 27	NP_001332893.1
	DHX29	NM_001345965.2		c.1948G>C	p.Glu650Gln	missense	Exon 25 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.3856G>C	p.Glu1286Gln	missense	Exon 25 of 27	ENSP00000251636.5	Q7Z478
	DHX29	ENST00000504778.5	TSL:1	n.4064G>C		non_coding_transcript_exon	Exon 25 of 27
	DHX29	ENST00000867273.1		c.3874G>C	p.Glu1292Gln	missense	Exon 25 of 27	ENSP00000537332.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1425422 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 711566

African (AFR) AF: 0.00 AC: 0 AN: 32740

American (AMR) AF: 0.00 AC: 0 AN: 44318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25872

East Asian (EAS) AF: 0.00 AC: 0 AN: 39350

South Asian (SAS) AF: 0.00 AC: 0 AN: 85266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079638

Other (OTH) AF: 0.00 AC: 0 AN: 59182

GnomAD4 genome Cov.: 32

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	0.57
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.3	T
MutationAssessor	Benign	1.5	L
PhyloP100		7.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.40
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.023	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.39
gMVP		0.47
Mutation Taster		=79/21	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-54557300;