Variant 17-42104881-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024119.3(DHX58):c.1448C>T(p.Ala483Val) variant causes a missense change involving the alteration of a conserved nucleotide. 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.09

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]

DHX58 links:

DHX58 (HGNC:):

DHX58 links:

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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
DHX58	NM_024119.3 linkuse as main transcript	c.1448C>T	p.Ala483Val	missense_variant	11/14	ENST00000251642.8	NP_077024.2	Q96C10A0A024R1Y5
DHX58	XM_047436724.1 linkuse as main transcript	c.1448C>T	p.Ala483Val	missense_variant	11/14		XP_047292680.1
DHX58	XM_047436725.1 linkuse as main transcript	c.1448C>T	p.Ala483Val	missense_variant	11/14		XP_047292681.1
DHX58	XM_047436726.1 linkuse as main transcript	c.1448C>T	p.Ala483Val	missense_variant	11/12		XP_047292682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DHX58	ENST00000251642.8 linkuse as main transcript	c.1448C>T	p.Ala483Val	missense_variant	11/14	1	NM_024119.3	ENSP00000251642.3	Q96C10
DHX58	ENST00000586522.5 linkuse as main transcript	n.1630C>T		non_coding_transcript_exon_variant	11/12	2
DHX58	ENST00000589979.1 linkuse as main transcript	n.26C>T		non_coding_transcript_exon_variant	1/3	3		ENSP00000467470.1	K7EPP0
DHX58	ENST00000590637.1 linkuse as main transcript	n.442C>T		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251306

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135870

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 submitter

clinical testing

Ambry Genetics

May 09, 2023

The c.1448C>T (p.A483V) alteration is located in exon 11 (coding exon 9) of the DHX58 gene. This alteration results from a C to T substitution at nucleotide position 1448, causing the alanine (A) at amino acid position 483 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

0.28

BayesDel_addAF

Uncertain

0.037

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

Eigen

Benign

-0.014

Eigen_PC

Benign

0.11

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.77

M_CAP

Benign

0.063

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.0

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.7

REVEL

Uncertain

0.31

Sift

Uncertain

0.016

Sift4G

Benign

0.073

Polyphen

0.48

Vest4

0.80

MutPred

0.34

Gain of sheet (P = 0.1208);

MVP

0.57

MPC

0.39

ClinPred

0.79

GERP RS

5.7

Varity_R

0.11

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over