Variant 6-30655292-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_003587.5(DHX16):c.2706T>C(p.Phe902Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 1,614,166 control chromosomes in the GnomAD database, including 268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.011 ( 16 hom., cov: 32)

Exomes 𝑓: 0.016 ( 252 hom. )

Consequence

DHX16
NM_003587.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.413

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 6-30655292-A-G is Benign according to our data. Variant chr6-30655292-A-G is described in ClinVar as [Benign]. Clinvar id is 3056294.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.413 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0112 (1709/152294) while in subpopulation NFE AF= 0.0184 (1249/68024). AF 95% confidence interval is 0.0175. There are 16 homozygotes in gnomad4. There are 782 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1709 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHX16	NM_003587.5 link	c.2706T>C	p.Phe902Phe	synonymous_variant	Exon 18 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.2706T>C	p.Phe902Phe	synonymous_variant	Exon 18 of 20	1	NM_003587.5	ENSP00000365625.3		O60231
DHX16	ENST00000376437.9 link	c.1263T>C	p.Phe421Phe	synonymous_variant	Exon 10 of 12	1		ENSP00000365620.5		Q5SQH5

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1708

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00309

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0226

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0183

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.0116

AC:

2910

AN:

251290

Hom.:

AF XY:

0.0116

AC XY:

1569

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.00253

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.0228

Gnomad NFE exome

AF:

0.0188

Gnomad OTH exome

AF:

0.00913

GnomAD4 exome

AF:

0.0163

AC:

23859

AN:

1461872

Hom.:

252

Cov.:

AF XY:

0.0156

AC XY:

11319

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00215

Gnomad4 AMR exome

AF:

0.00407

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.00126

Gnomad4 FIN exome

AF:

0.0235

Gnomad4 NFE exome

AF:

0.0193

Gnomad4 OTH exome

AF:

0.0130

GnomAD4 genome

AF:

0.0112

AC:

1709

AN:

152294

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

782

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00308

Gnomad4 AMR

AF:

0.00445

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0226

Gnomad4 NFE

AF:

0.0184

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.0163

Hom.:

Bravo

AF:

0.0101

EpiCase

AF:

0.0148

EpiControl

AF:

0.0133

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DHX16-related disorder

Benign:1

Sep 13, 2021

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

BayesDel_noAF

Benign

-0.59

CADD

Benign

3.5

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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