chr5-55261418-C-T

Variant names:

• chr5-55261418-C-T
• rs1561133245
• NM_019030.4:c.3910G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019030.4(DHX29):​c.3910G>A​(p.Val1304Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000211 in 1,425,156 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DHX29 NM_019030.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.24
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20143333).

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.3910G>A	p.Val1304Ile	missense	Exon 25 of 27	NP_061903.2	Q7Z478
	DHX29	NM_001345964.2		c.3757G>A	p.Val1253Ile	missense	Exon 25 of 27	NP_001332893.1
	DHX29	NM_001345965.2		c.2002G>A	p.Val668Ile	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.3910G>A	p.Val1304Ile	missense	Exon 25 of 27	ENSP00000251636.5	Q7Z478
	DHX29	ENST00000504778.5	TSL:1	n.4118G>A		non_coding_transcript_exon	Exon 25 of 27
	DHX29	ENST00000867273.1		c.3928G>A	p.Val1310Ile	missense	Exon 25 of 27	ENSP00000537332.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250590 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1425156 Hom.: 0 Cov.: 24 AF XY: 0.00000141 AC XY: 1 AN XY: 711598

African (AFR) AF: 0.00 AC: 0 AN: 32720

American (AMR) AF: 0.00 AC: 0 AN: 44430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25890

East Asian (EAS) AF: 0.00 AC: 0 AN: 39352

South Asian (SAS) AF: 0.00 AC: 0 AN: 85320

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1079230

Other (OTH) AF: 0.00 AC: 0 AN: 59168

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	Benign	0.10
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		4.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.18
Sift	Benign	0.21	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.85	P
Vest4		0.17
MutPred		0.31		Gain of catalytic residue at V1304 (P = 0.1676)
MVP		0.25
MPC		0.29
ClinPred		0.88	D
GERP RS		5.9
Varity_R		0.11
gMVP		0.16
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

dbSNP: rs1561133245; hg19: chr5-54557246;