Variant chr16-21039887-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001347886.2(DNAH3):c.4557C>G(p.Ile1519Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,612,088 control chromosomes in the GnomAD database, including 10,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1526 hom., cov: 31)

Exomes 𝑓: 0.11 ( 8722 hom. )

Consequence

DNAH3
NM_001347886.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.540

Variant links:

Genes affected

DNAH3 (HGNC:2949): (dynein axonemal heavy chain 3) This gene belongs to the dynein family, whose members encode large proteins that are constituents of the microtubule-associated motor protein complex. This complex is composed of dynein heavy, intermediate and light chains, which can be axonemal or cytoplasmic. This protein is an axonemal dynein heavy chain. It is involved in producing force for ciliary beating by using energy from ATP hydrolysis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Dec 2016]

DNAH3 links:

DNAH3 (HGNC:):

DNAH3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018554926).

BP6

Variant 16-21039887-G-C is Benign according to our data. Variant chr16-21039887-G-C is described in ClinVar as [Benign]. Clinvar id is 402723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH3	NM_001347886.2 linkuse as main transcript	c.4557C>G	p.Ile1519Met	missense_variant	33/62	ENST00000698260.1	NP_001334815.1	Q8TD57A0A8V8TLI9B4E1S1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH3	ENST00000698260.1 linkuse as main transcript	c.4557C>G	p.Ile1519Met	missense_variant	33/62		NM_001347886.2	ENSP00000513632.1		A0A8V8TLI9

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20013

AN:

152074

Hom.:

1525

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.0859

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.0718

Gnomad FIN

AF:

0.0967

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.120

GnomAD3 exomes

AF:

0.109

AC:

27317

AN:

251120

Hom.:

1627

AF XY:

0.108

AC XY:

14657

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.207

Gnomad AMR exome

AF:

0.0827

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.151

Gnomad SAS exome

AF:

0.0812

Gnomad FIN exome

AF:

0.0936

Gnomad NFE exome

AF:

0.103

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.106

AC:

154045

AN:

1459896

Hom.:

8722

Cov.:

AF XY:

0.105

AC XY:

76073

AN XY:

726352

show subpopulations

Gnomad4 AFR exome

AF:

0.211

Gnomad4 AMR exome

AF:

0.0850

Gnomad4 ASJ exome

AF:

0.137

Gnomad4 EAS exome

AF:

0.160

Gnomad4 SAS exome

AF:

0.0779

Gnomad4 FIN exome

AF:

0.0909

Gnomad4 NFE exome

AF:

0.103

Gnomad4 OTH exome

AF:

0.112

GnomAD4 genome

AF:

0.132

AC:

20022

AN:

152192

Hom.:

1526

Cov.:

AF XY:

0.130

AC XY:

9700

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.198

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.136

Gnomad4 EAS

AF:

0.148

Gnomad4 SAS

AF:

0.0715

Gnomad4 FIN

AF:

0.0967

Gnomad4 NFE

AF:

0.107

Gnomad4 OTH

AF:

0.119

Alfa

AF:

0.113

Hom.:

797

Bravo

AF:

0.137

TwinsUK

AF:

0.0974

AC:

361

ALSPAC

AF:

0.0924

AC:

356

ESP6500AA

AF:

0.199

AC:

875

ESP6500EA

AF:

0.101

AC:

868

ExAC

AF:

0.110

AC:

13323

Asia WGS

AF:

0.122

AC:

423

AN:

3478

EpiCase

AF:

0.108

EpiControl

AF:

0.104

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.98

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.9

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.33

Sift

Uncertain

0.0030

Polyphen

1.0

Vest4

0.76

MPC

0.49

ClinPred

0.063

GERP RS

2.3

Varity_R

0.85

gMVP

0.64

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