Variant 2-38798357-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_198963.3(DHX57):c.4103C>T(p.Thr1368Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00517 in 1,614,078 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0053 ( 36 hom. )

Consequence

DHX57
NM_198963.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.21

Variant links:

Genes affected

DHX57 (HGNC:20086): (DExH-box helicase 57) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

DHX57 links:

DHX57 (HGNC:):

DHX57 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008805484).

BP6

Variant 2-38798357-G-A is Benign according to our data. Variant chr2-38798357-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2650841.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHX57	NM_198963.3 linkuse as main transcript	c.4103C>T	p.Thr1368Met	missense_variant	24/24	ENST00000457308.6	NP_945314.1	Q6P158-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHX57	ENST00000457308.6 linkuse as main transcript	c.4103C>T	p.Thr1368Met	missense_variant	24/24	1	NM_198963.3	ENSP00000405111.2		Q6P158-1

Frequencies

GnomAD3 genomes

AF:

0.00348

AC:

529

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000989

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.00302

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00536

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00387

AC:

973

AN:

251248

Hom.:

AF XY:

0.00418

AC XY:

568

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.00217

Gnomad ASJ exome

AF:

0.00347

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00445

Gnomad FIN exome

AF:

0.00254

Gnomad NFE exome

AF:

0.00558

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00534

AC:

7813

AN:

1461784

Hom.:

Cov.:

AF XY:

0.00539

AC XY:

3919

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.000837

Gnomad4 AMR exome

AF:

0.00221

Gnomad4 ASJ exome

AF:

0.00375

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00492

Gnomad4 FIN exome

AF:

0.00361

Gnomad4 NFE exome

AF:

0.00606

Gnomad4 OTH exome

AF:

0.00371

GnomAD4 genome

AF:

0.00347

AC:

529

AN:

152294

Hom.:

Cov.:

AF XY:

0.00358

AC XY:

267

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000986

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.00302

Gnomad4 NFE

AF:

0.00537

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00543

Hom.:

Bravo

AF:

0.00312

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00417

AC:

506

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00447

EpiControl

AF:

0.00498

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

DHX57: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.035

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.75

M_CAP

Benign

0.0034

MetaRNN

Benign

0.0088

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.2

PrimateAI

Benign

0.32

Sift4G

Benign

0.15

Polyphen

0.026

Vest4

0.086

MVP

0.44

ClinPred

0.0033

GERP RS

2.6

Varity_R

0.019

gMVP

0.26

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