Genetic Variant NM_024119.3:c.1597C>A (chr17-42103765-G-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_024119.3(DHX58):c.1597C>A(p.Arg533Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DHX58
NM_024119.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.12

Publications

3 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: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP7

Synonymous conserved (PhyloP=2.12 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHX58	NM_024119.3 link	c.1597C>A	p.Arg533Arg	synonymous_variant	Exon 12 of 14	ENST00000251642.8	NP_077024.2	Q96C10A0A024R1Y5
DHX58	XM_047436724.1 link	c.1597C>A	p.Arg533Arg	synonymous_variant	Exon 12 of 14		XP_047292680.1
DHX58	XM_047436725.1 link	c.1597C>A	p.Arg533Arg	synonymous_variant	Exon 12 of 14		XP_047292681.1
DHX58	XM_047436726.1 link	c.1563+1001C>A		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.1597C>A	p.Arg533Arg	synonymous_variant	Exon 12 of 14	1	NM_024119.3	ENSP00000251642.3	Q96C10
DHX58	ENST00000586522.5 link	n.1779C>A		non_coding_transcript_exon_variant	Exon 12 of 12	2
DHX58	ENST00000590637.1 link	n.591C>A		non_coding_transcript_exon_variant	Exon 4 of 4	5
DHX58	ENST00000589979.1 link	n.141+1001C>A		intron_variant	Intron 1 of 2	3		ENSP00000467470.1	K7EPP0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

247860

AF XY:

0.00000743

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000206

AC:

AN:

1458066

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725524

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.0000447

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5304

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111926

Other (OTH)

AF:

0.00

AC:

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.5

(source)

DANN

Benign

0.40

PhyloP100

2.1

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over