Genetic Variant DHX15:p.Phe118Phe (chr4-24576396-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001358.3(DHX15):c.354C>T(p.Phe118Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00352 in 1,614,192 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 24 hom. )

Consequence

DHX15
NM_001358.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.33

Variant links:

Genes affected

DHX15 (HGNC:2738): (DEAH-box helicase 15) The protein encoded by this gene is a putative ATP-dependent RNA helicase implicated in pre-mRNA splicing. [provided by RefSeq, Jul 2008]

DHX15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 4-24576396-G-A is Benign according to our data. Variant chr4-24576396-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654696.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.33 with no splicing effect.

BS2

High AC in GnomAd4 at 486 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHX15	NM_001358.3 link	c.354C>T	p.Phe118Phe	synonymous_variant	Exon 2 of 14	ENST00000336812.5	NP_001349.2	O43143
DHX15	XM_047449698.1 link	c.354C>T	p.Phe118Phe	synonymous_variant	Exon 2 of 11		XP_047305654.1
DHX15	XM_047449699.1 link	c.354C>T	p.Phe118Phe	synonymous_variant	Exon 2 of 11		XP_047305655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DHX15	ENST00000336812.5 link	c.354C>T	p.Phe118Phe	synonymous_variant	Exon 2 of 14	1	NM_001358.3	ENSP00000336741.4	O43143
DHX15	ENST00000511553.5 link	n.*73C>T		downstream_gene_variant		4
DHX15	ENST00000513092.1 link	n.*154C>T		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00320

AC:

487

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00931

Gnomad FIN

AF:

0.0141

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00381

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00384

AC:

966

AN:

251476

Hom.:

AF XY:

0.00430

AC XY:

584

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000954

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00807

Gnomad FIN exome

AF:

0.0142

Gnomad NFE exome

AF:

0.00309

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00356

AC:

5201

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00378

AC XY:

2748

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000984

Gnomad4 ASJ exome

AF:

0.000650

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00836

Gnomad4 FIN exome

AF:

0.0143

Gnomad4 NFE exome

AF:

0.00312

Gnomad4 OTH exome

AF:

0.00255

GnomAD4 genome

AF:

0.00319

AC:

486

AN:

152306

Hom.:

Cov.:

AF XY:

0.00360

AC XY:

268

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00932

Gnomad4 FIN

AF:

0.0141

Gnomad4 NFE

AF:

0.00379

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00244

Hom.:

Bravo

AF:

0.00171

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00256

EpiControl

AF:

0.00255

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DHX15: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.8

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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