17-42102239-T-A

Variant names:

• chr17-42102239-T-A
• rs1395880803
• NM_024119.3:c.1828A>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024119.3(DHX58):​c.1828A>T​(p.Ile610Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 3.67
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.809

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHX58	NM_024119.3	c.1828A>T	p.Ile610Phe	missense_variant	Exon 13 of 14	ENST00000251642.8	NP_077024.2
DHX58	XM_047436724.1	c.1828A>T	p.Ile610Phe	missense_variant	Exon 13 of 14		XP_047292680.1
DHX58	XM_047436725.1	c.1828A>T	p.Ile610Phe	missense_variant	Exon 13 of 14		XP_047292681.1
DHX58	XM_047436726.1	c.*62A>T		3_prime_UTR_variant	Exon 12 of 12		XP_047292682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHX58	ENST00000251642.8	c.1828A>T	p.Ile610Phe	missense_variant	Exon 13 of 14	1	NM_024119.3	ENSP00000251642.3
DHX58	ENST00000589979.1	n.*62A>T		non_coding_transcript_exon_variant	Exon 2 of 3	3		ENSP00000467470.1
DHX58	ENST00000592024.1	n.571A>T		non_coding_transcript_exon_variant	Exon 1 of 2	2
DHX58	ENST00000589979.1	n.*62A>T		3_prime_UTR_variant	Exon 2 of 3	3		ENSP00000467470.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1828A>T (p.I610F) alteration is located in exon 13 (coding exon 11) of the DHX58 gene. This alteration results from a A to T substitution at nucleotide position 1828, causing the isoleucine (I) at amino acid position 610 to be replaced by a phenylalanine (F). 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	0.43
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.068	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		3.7
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.034	D
Polyphen		1.0	D
Vest4		0.66
MutPred		0.54		Loss of sheet (P = 0.0011);
MVP		0.87
MPC		1.1
ClinPred		0.99	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.31
gMVP		0.89

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

Other links and lift over

dbSNP: rs1395880803; hg19: chr17-40254257;