17-42102221-C-A

Variant summary

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

The NM_024119.3(DHX58):​c.1846G>T​(p.Gly616Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

DHX58
NM_024119.3 missense

Scores

7
6
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.45
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
DHX58NM_024119.3 linkuse as main transcriptc.1846G>T p.Gly616Trp missense_variant 13/14 ENST00000251642.8 NP_077024.2 Q96C10A0A024R1Y5
DHX58XM_047436724.1 linkuse as main transcriptc.1846G>T p.Gly616Trp missense_variant 13/14 XP_047292680.1
DHX58XM_047436725.1 linkuse as main transcriptc.1846G>T p.Gly616Trp missense_variant 13/14 XP_047292681.1
DHX58XM_047436726.1 linkuse as main transcriptc.*80G>T 3_prime_UTR_variant 12/12 XP_047292682.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DHX58ENST00000251642.8 linkuse as main transcriptc.1846G>T p.Gly616Trp missense_variant 13/141 NM_024119.3 ENSP00000251642.3 Q96C10
DHX58ENST00000589979.1 linkuse as main transcriptn.*80G>T non_coding_transcript_exon_variant 2/33 ENSP00000467470.1 K7EPP0
DHX58ENST00000592024.1 linkuse as main transcriptn.589G>T non_coding_transcript_exon_variant 1/22
DHX58ENST00000589979.1 linkuse as main transcriptn.*80G>T 3_prime_UTR_variant 2/33 ENSP00000467470.1 K7EPP0

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152206
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000314
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251438
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461874
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152206
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.000314
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000680
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 21, 2024The c.1846G>T (p.G616W) alteration is located in exon 13 (coding exon 11) of the DHX58 gene. This alteration results from a G to T substitution at nucleotide position 1846, causing the glycine (G) at amino acid position 616 to be replaced by a tryptophan (W). 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
0.53
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.12
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.52
D
Eigen
Pathogenic
0.75
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.83
T
M_CAP
Uncertain
0.14
D
MetaRNN
Uncertain
0.62
D
MetaSVM
Benign
-0.45
T
MutationAssessor
Pathogenic
3.1
M
PrimateAI
Benign
0.43
T
PROVEAN
Pathogenic
-6.0
D
REVEL
Uncertain
0.34
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.41
MVP
0.85
MPC
0.94
ClinPred
0.98
D
GERP RS
5.5
Varity_R
0.40
gMVP
0.68

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs145445108; hg19: chr17-40254239; API