rs193920824

Positions:

• chr5-55290250-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019030.4(DHX29):​c.875A>T​(p.Glu292Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DHX29 NM_019030.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.684

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)

LOC105378973 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.081155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHX29	NM_019030.4	c.875A>T	p.Glu292Val	missense_variant	7/27	ENST00000251636.10
LOC105378973	XR_001742666.2	n.2047-4590T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHX29	ENST00000251636.10	c.875A>T	p.Glu292Val	missense_variant	7/27	1	NM_019030.4	P1
DHX29	ENST00000504778.5	n.996A>T		non_coding_transcript_exon_variant	7/27	1
CCNO-DT	ENST00000506435.1	n.409-4590T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.070	T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.032
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.081	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;.
MutationTaster	Benign	0.92	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.2	N;.
REVEL	Benign	0.047
Sift	Benign	0.24	T;.
Sift4G	Benign	0.27	T;T
Polyphen		0.0	B;.
Vest4		0.23
MutPred		0.27		Loss of ubiquitination at K296 (P = 0.0352);Loss of ubiquitination at K296 (P = 0.0352);
MVP		0.57
MPC		0.28
ClinPred		0.47	T
GERP RS		5.4
Varity_R		0.072
gMVP		0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs193920824; hg19: chr5-54586078; COSMIC: COSV52422799;