Variant 16-72096226-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000268482.8(DHX38):c.69T>C(p.Gly23=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 1,614,078 control chromosomes in the GnomAD database, including 2,207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 164 hom., cov: 32)

Exomes 𝑓: 0.050 ( 2043 hom. )

Consequence

DHX38
ENST00000268482.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.83

Variant links:

Genes affected

DHX38 (HGNC:17211): (DEAH-box helicase 38) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. The protein encoded by this gene is a member of the DEAD/H box family of splicing factors. This protein resembles yeast Prp16 more closely than other DEAD/H family members. It is an ATPase and essential for the catalytic step II in pre-mRNA splicing process. [provided by RefSeq, Jul 2008]

DHX38 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 16-72096226-T-C is Benign according to our data. Variant chr16-72096226-T-C is described in ClinVar as [Benign]. Clinvar id is 1167323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.83 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHX38	NM_014003.4 linkuse as main transcript	c.69T>C	p.Gly23=	synonymous_variant	2/27	ENST00000268482.8	NP_054722.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHX38	ENST00000268482.8 linkuse as main transcript	c.69T>C	p.Gly23=	synonymous_variant	2/27	1	NM_014003.4	ENSP00000268482	P1	Q92620-1
DHX38	ENST00000566794.5 linkuse as main transcript	c.69T>C	p.Gly23=	synonymous_variant	2/3	4		ENSP00000455939
DHX38	ENST00000566489.1 linkuse as main transcript	c.69T>C	p.Gly23=	synonymous_variant	3/4	4		ENSP00000457887
DHX38	ENST00000579387.5 linkuse as main transcript	c.69T>C	p.Gly23=	synonymous_variant, NMD_transcript_variant	2/12	5		ENSP00000462149

Frequencies

GnomAD3 genomes

AF:

0.0443

AC:

6742

AN:

152172

Hom.:

157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0316

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0387

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.0492

Gnomad SAS

AF:

0.0292

Gnomad FIN

AF:

0.0300

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0566

Gnomad OTH

AF:

0.0532

GnomAD3 exomes

AF:

0.0431

AC:

10832

AN:

251146

Hom.:

291

AF XY:

0.0434

AC XY:

5899

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.0312

Gnomad AMR exome

AF:

0.0347

Gnomad ASJ exome

AF:

0.0344

Gnomad EAS exome

AF:

0.0511

Gnomad SAS exome

AF:

0.0280

Gnomad FIN exome

AF:

0.0341

Gnomad NFE exome

AF:

0.0529

Gnomad OTH exome

AF:

0.0401

GnomAD4 exome

AF:

0.0502

AC:

73330

AN:

1461788

Hom.:

2043

Cov.:

AF XY:

0.0496

AC XY:

36082

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.0317

Gnomad4 AMR exome

AF:

0.0343

Gnomad4 ASJ exome

AF:

0.0315

Gnomad4 EAS exome

AF:

0.0497

Gnomad4 SAS exome

AF:

0.0279

Gnomad4 FIN exome

AF:

0.0344

Gnomad4 NFE exome

AF:

0.0544

Gnomad4 OTH exome

AF:

0.0485

GnomAD4 genome

AF:

0.0445

AC:

6774

AN:

152290

Hom.:

164

Cov.:

AF XY:

0.0433

AC XY:

3228

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0323

Gnomad4 AMR

AF:

0.0387

Gnomad4 ASJ

AF:

0.0311

Gnomad4 EAS

AF:

0.0493

Gnomad4 SAS

AF:

0.0294

Gnomad4 FIN

AF:

0.0300

Gnomad4 NFE

AF:

0.0566

Gnomad4 OTH

AF:

0.0531

Alfa

AF:

0.0510

Hom.:

121

Bravo

AF:

0.0445

Asia WGS

AF:

0.0560

AC:

195

AN:

3478

EpiCase

AF:

0.0538

EpiControl

AF:

0.0542

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 03, 2022	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.48

DANN

Benign

0.50

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.

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