17-42104860-A-G

Position:

• chr17-42104860-A-G

Variant summary

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

The NM_024119.3(DHX58):​c.1469T>C​(p.Leu490Pro) 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)
• Consequence: DHX58 NM_024119.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.08

Genes affected

DHX58 (HGNC:29517): (DExH-box helicase 58) Enables double-stranded RNA binding activity; single-stranded RNA binding activity; and zinc ion binding activity. Involved in negative regulation of defense response and negative regulation of type I interferon production. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DHX58 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHX58	NM_024119.3	c.1469T>C	p.Leu490Pro	missense_variant	11/14	ENST00000251642.8	NP_077024.2
DHX58	XM_047436724.1	c.1469T>C	p.Leu490Pro	missense_variant	11/14		XP_047292680.1
DHX58	XM_047436725.1	c.1469T>C	p.Leu490Pro	missense_variant	11/14		XP_047292681.1
DHX58	XM_047436726.1	c.1469T>C	p.Leu490Pro	missense_variant	11/12		XP_047292682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHX58	ENST00000251642.8	c.1469T>C	p.Leu490Pro	missense_variant	11/14	1	NM_024119.3	ENSP00000251642.3
DHX58	ENST00000586522.5	n.1651T>C		non_coding_transcript_exon_variant	11/12	2
DHX58	ENST00000589979.1	n.47T>C		non_coding_transcript_exon_variant	1/3	3		ENSP00000467470.1
DHX58	ENST00000590637.1	n.463T>C		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2024

The c.1469T>C (p.L490P) alteration is located in exon 11 (coding exon 9) of the DHX58 gene. This alteration results from a T to C substitution at nucleotide position 1469, causing the leucine (L) at amino acid position 490 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.22
Sift	Uncertain	0.013	D
Sift4G	Benign	0.079	T
Polyphen		0.98	D
Vest4		0.64
MutPred		0.55		Gain of glycosylation at L490 (P = 0.01);
MVP		0.60
MPC		0.88
ClinPred		0.97	D
GERP RS		4.6
Varity_R		0.50
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-40256878;