6-30656464-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_003587.5(DHX16):c.2357A>G(p.Tyr786Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00325 in 1,614,060 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0019 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 98 hom. )

Consequence

DHX16
NM_003587.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.93

Variant links:

Genes affected

DHX16 (HGNC:2739): (DEAH-box helicase 16) 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. This gene encodes a DEAD box protein, which is a functional homolog of fission yeast Prp8 protein involved in cell cycle progression. This gene is mapped to the MHC region on chromosome 6p21.3, a region where many malignant, genetic and autoimmune disease genes are linked. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2018]

DHX16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042455494).

BP6

Variant 6-30656464-T-C is Benign according to our data. Variant chr6-30656464-T-C is described in ClinVar as [Benign]. Clinvar id is 3056890.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0019 (289/152174) while in subpopulation SAS AF= 0.042 (202/4814). AF 95% confidence interval is 0.0372. There are 5 homozygotes in gnomad4. There are 206 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 289 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHX16	NM_003587.5 link	c.2357A>G	p.Tyr786Cys	missense_variant	Exon 15 of 20	ENST00000376442.8	NP_003578.2	O60231Q5SQH4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHX16	ENST00000376442.8 link	c.2357A>G	p.Tyr786Cys	missense_variant	Exon 15 of 20	1	NM_003587.5	ENSP00000365625.3		O60231
DHX16	ENST00000376437.9 link	c.914A>G	p.Tyr305Cys	missense_variant	Exon 7 of 12	1		ENSP00000365620.5		Q5SQH5

Frequencies

GnomAD3 genomes

AF:

0.00189

AC:

288

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.0419

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000971

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00563

AC:

1415

AN:

251450

Hom.:

AF XY:

0.00781

AC XY:

1062

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.000489

Gnomad SAS exome

AF:

0.0410

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00109

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00339

AC:

4960

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00461

AC XY:

3354

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.0408

Gnomad4 FIN exome

AF:

0.000393

Gnomad4 NFE exome

AF:

0.00102

Gnomad4 OTH exome

AF:

0.00320

GnomAD4 genome

AF:

0.00190

AC:

289

AN:

152174

Hom.:

Cov.:

AF XY:

0.00277

AC XY:

206

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.0420

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000971

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.000876

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00624

AC:

758

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DHX16-related disorder

Benign:1

Oct 31, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.012

.;T

Eigen

Benign

0.043

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.80

MetaRNN

Benign

0.0042

T;T

MetaSVM

Benign

-0.45

MutationAssessor

Benign

0.34

.;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.11

Sift

Benign

0.16

T;T

Sift4G

Uncertain

0.040

D;T

Polyphen

0.81

P;P

Vest4

0.44

MVP

0.48

MPC

0.75

ClinPred

0.025

GERP RS

5.1

Varity_R

0.24

gMVP

0.75

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