Variant chr16-20985659-G-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 NM_001347886.2(DNAH3):c.6945C>G(p.Leu2315=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 1,614,154 control chromosomes in the GnomAD database, including 2,001 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 131 hom., cov: 31)

Exomes 𝑓: 0.047 ( 1870 hom. )

Consequence

DNAH3
NM_001347886.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0920

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:

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=-0.53).

BP6

Variant 16-20985659-G-C is Benign according to our data. Variant chr16-20985659-G-C is described in ClinVar as [Benign]. Clinvar id is 402720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.092 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0517 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.6945C>G	p.Leu2315=	synonymous_variant	48/62	ENST00000698260.1	NP_001334815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH3	ENST00000698260.1 linkuse as main transcript	c.6945C>G	p.Leu2315=	synonymous_variant	48/62		NM_001347886.2	ENSP00000513632	P1
DNAH3	ENST00000261383.3 linkuse as main transcript	c.7083C>G	p.Leu2361=	synonymous_variant	48/62	1		ENSP00000261383		Q8TD57-1
DNAH3	ENST00000685858.1 linkuse as main transcript	c.7125C>G	p.Leu2375=	synonymous_variant	48/62			ENSP00000508756

Frequencies

GnomAD3 genomes

AF:

0.0355

AC:

5398

AN:

152154

Hom.:

131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00922

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0409

Gnomad ASJ

AF:

0.0600

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.0352

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0531

Gnomad OTH

AF:

0.0425

GnomAD3 exomes

AF:

0.0364

AC:

9161

AN:

251422

Hom.:

220

AF XY:

0.0375

AC XY:

5092

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.00548

Gnomad AMR exome

AF:

0.0280

Gnomad ASJ exome

AF:

0.0580

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0156

Gnomad FIN exome

AF:

0.0380

Gnomad NFE exome

AF:

0.0527

Gnomad OTH exome

AF:

0.0365

GnomAD4 exome

AF:

0.0474

AC:

69321

AN:

1461882

Hom.:

1870

Cov.:

AF XY:

0.0468

AC XY:

34061

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00687

Gnomad4 AMR exome

AF:

0.0291

Gnomad4 ASJ exome

AF:

0.0598

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0159

Gnomad4 FIN exome

AF:

0.0370

Gnomad4 NFE exome

AF:

0.0540

Gnomad4 OTH exome

AF:

0.0438

GnomAD4 genome

AF:

0.0354

AC:

5396

AN:

152272

Hom.:

131

Cov.:

AF XY:

0.0346

AC XY:

2579

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00919

Gnomad4 AMR

AF:

0.0409

Gnomad4 ASJ

AF:

0.0600

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0143

Gnomad4 FIN

AF:

0.0352

Gnomad4 NFE

AF:

0.0531

Gnomad4 OTH

AF:

0.0416

Alfa

AF:

0.0409

Hom.:

Bravo

AF:

0.0348

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 10, 2018	- -

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, silent -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

3.9

DANN

Benign

0.77

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