rs1260663466

Variant names:

• chr5-55262899-C-A
• rs1260663466
• NM_019030.4:c.3559G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-55262899-C-A
• chr5-55262899-C-T

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.3559G>T​(p.Ala1187Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1187T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DHX29 NM_019030.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.92
• 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=0.16276944).

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.3559G>T	p.Ala1187Ser	missense	Exon 24 of 27	NP_061903.2	Q7Z478
	DHX29	NM_001345964.2		c.3406G>T	p.Ala1136Ser	missense	Exon 24 of 27	NP_001332893.1
	DHX29	NM_001345965.2		c.1651G>T	p.Ala551Ser	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.3559G>T	p.Ala1187Ser	missense	Exon 24 of 27	ENSP00000251636.5	Q7Z478
	DHX29	ENST00000504778.5	TSL:1	n.3767G>T		non_coding_transcript_exon	Exon 24 of 27
	DHX29	ENST00000867273.1		c.3577G>T	p.Ala1193Ser	missense	Exon 24 of 27	ENSP00000537332.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.033
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.71	N
PhyloP100		3.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.74	N
REVEL	Benign	0.080
Sift	Benign	0.43	T
Sift4G	Benign	0.49	T
Polyphen		0.044	B
Vest4		0.35
MutPred		0.34		Gain of disorder (P = 0.0183)
MVP		0.33
MPC		0.24
ClinPred		0.58	D
GERP RS		5.4
Varity_R		0.099
gMVP		0.20
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1260663466; hg19: chr5-54558727;