17-42103761-G-A

Variant names:

• chr17-42103761-G-A
• rs202112076
• NM_024119.3:c.1601C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024119.3(DHX58):​c.1601C>T​(p.Ala534Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000503 in 1,610,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: DHX58 NM_024119.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.373
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055303544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHX58	NM_024119.3	c.1601C>T	p.Ala534Val	missense_variant	Exon 12 of 14	ENST00000251642.8	NP_077024.2
DHX58	XM_047436724.1	c.1601C>T	p.Ala534Val	missense_variant	Exon 12 of 14		XP_047292680.1
DHX58	XM_047436725.1	c.1601C>T	p.Ala534Val	missense_variant	Exon 12 of 14		XP_047292681.1
DHX58	XM_047436726.1	c.1563+1005C>T		intron_variant	Intron 11 of 11		XP_047292682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHX58	ENST00000251642.8	c.1601C>T	p.Ala534Val	missense_variant	Exon 12 of 14	1	NM_024119.3	ENSP00000251642.3
DHX58	ENST00000586522.5	n.1783C>T		non_coding_transcript_exon_variant	Exon 12 of 12	2
DHX58	ENST00000590637.1	n.595C>T		non_coding_transcript_exon_variant	Exon 4 of 4	5
DHX58	ENST00000589979.1	n.141+1005C>T		intron_variant	Intron 1 of 2	3		ENSP00000467470.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152236 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000161 AC: 4 AN: 248332 AF XY: 0.0000223

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: 0.0000354

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000507 AC: 74 AN: 1458642 Hom.: 0 Cov.: 31 AF XY: 0.0000482 AC XY: 35 AN XY: 725756

African (AFR) AF: 0.000209 AC: 7 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.0000197 AC: 1 AN: 50806

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5382

European-Non Finnish (NFE) AF: 0.0000549 AC: 61 AN: 1111926

Other (OTH) AF: 0.0000663 AC: 4 AN: 60320

GnomAD4 genome AF: 0.0000459 AC: 7 AN: 152354 Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5 AN XY: 74520

African (AFR) AF: 0.0000722 AC: 3 AN: 41580

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000540 Hom.: 0

Bravo AF: 0.0000302

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1601C>T (p.A534V) alteration is located in exon 12 (coding exon 10) of the DHX58 gene. This alteration results from a C to T substitution at nucleotide position 1601, causing the alanine (A) at amino acid position 534 to be replaced by a valine (V). 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	Benign	0.083
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.73
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.37
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.035
Sift	Benign	0.32	T
Sift4G	Benign	0.34	T
Polyphen		0.0020	B
Vest4		0.15
MutPred		0.36		Loss of loop (P = 0.0203);
MVP		0.19
MPC		0.24
ClinPred		0.070	T
GERP RS		3.5
Varity_R		0.024
gMVP		0.25
Mutation Taster		=97/3	polymorphism

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: rs202112076; hg19: chr17-40255779;