Genetic Variant DHX58:p.Arg544Leu (chr17-42103731-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024119.3(DHX58):c.1631G>T(p.Arg544Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R544Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DHX58
NM_024119.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.211

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17303339).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHX58	NM_024119.3 link	c.1631G>T	p.Arg544Leu	missense_variant	Exon 12 of 14	ENST00000251642.8	NP_077024.2	Q96C10A0A024R1Y5
DHX58	XM_047436724.1 link	c.1631G>T	p.Arg544Leu	missense_variant	Exon 12 of 14		XP_047292680.1
DHX58	XM_047436725.1 link	c.1631G>T	p.Arg544Leu	missense_variant	Exon 12 of 14		XP_047292681.1
DHX58	XM_047436726.1 link	c.1563+1035G>T		intron_variant	Intron 11 of 11		XP_047292682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DHX58	ENST00000251642.8 link	c.1631G>T	p.Arg544Leu	missense_variant	Exon 12 of 14	1	NM_024119.3	ENSP00000251642.3	Q96C10
DHX58	ENST00000586522.5 link	n.1813G>T		non_coding_transcript_exon_variant	Exon 12 of 12	2
DHX58	ENST00000590637.1 link	n.625G>T		non_coding_transcript_exon_variant	Exon 4 of 4	5
DHX58	ENST00000589979.1 link	n.141+1035G>T		intron_variant	Intron 1 of 2	3		ENSP00000467470.1	K7EPP0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461106

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726926

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52776

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111994

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Uncertain

0.47

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.79

M_CAP

Benign

0.014

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

PhyloP100

-0.21

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.054

Sift

Benign

0.16

Sift4G

Benign

0.44

Polyphen

0.89

Vest4

0.34

MutPred

0.39

Loss of loop (P = 0.0153);

MVP

0.34

MPC

0.54

ClinPred

0.60

GERP RS

-3.1

Varity_R

0.41

gMVP

0.56

Mutation Taster

=85/15

polymorphism

(source)

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

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17-42103731-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over