Variant rs3115446 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001347886.2(DNAH3):c.6378A>G(p.Lys2126=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,613,834 control chromosomes in the GnomAD database, including 181,144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.50 ( 19500 hom., cov: 32)

Exomes 𝑓: 0.47 ( 161644 hom. )

Consequence

DNAH3
NM_001347886.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.381

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 16-20997368-T-C is Benign according to our data. Variant chr16-20997368-T-C is described in ClinVar as [Benign]. Clinvar id is 402721.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.381 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH3	NM_001347886.2 linkuse as main transcript	c.6378A>G	p.Lys2126=	synonymous_variant	44/62	ENST00000698260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH3	ENST00000698260.1 linkuse as main transcript	c.6378A>G	p.Lys2126=	synonymous_variant	44/62		NM_001347886.2	P1
DNAH3	ENST00000261383.3 linkuse as main transcript	c.6516A>G	p.Lys2172=	synonymous_variant	44/62	1			Q8TD57-1
DNAH3	ENST00000685858.1 linkuse as main transcript	c.6558A>G	p.Lys2186=	synonymous_variant	44/62
DNAH3	ENST00000572640.5 linkuse as main transcript	n.3227A>G		non_coding_transcript_exon_variant	21/21	2

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76427

AN:

151922

Hom.:

19487

Cov.:

show subpopulations

Gnomad AFR

AF:

0.588

Gnomad AMI

AF:

0.445

Gnomad AMR

AF:

0.487

Gnomad ASJ

AF:

0.435

Gnomad EAS

AF:

0.491

Gnomad SAS

AF:

0.613

Gnomad FIN

AF:

0.501

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.464

GnomAD3 exomes

AF:

0.491

AC:

123414

AN:

251320

Hom.:

30744

AF XY:

0.495

AC XY:

67205

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.593

Gnomad AMR exome

AF:

0.473

Gnomad ASJ exome

AF:

0.439

Gnomad EAS exome

AF:

0.521

Gnomad SAS exome

AF:

0.603

Gnomad FIN exome

AF:

0.494

Gnomad NFE exome

AF:

0.452

Gnomad OTH exome

AF:

0.473

GnomAD4 exome

AF:

0.468

AC:

684345

AN:

1461794

Hom.:

161644

Cov.:

AF XY:

0.472

AC XY:

343167

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.590

Gnomad4 AMR exome

AF:

0.479

Gnomad4 ASJ exome

AF:

0.435

Gnomad4 EAS exome

AF:

0.495

Gnomad4 SAS exome

AF:

0.597

Gnomad4 FIN exome

AF:

0.493

Gnomad4 NFE exome

AF:

0.452

Gnomad4 OTH exome

AF:

0.481

GnomAD4 genome

AF:

0.503

AC:

76481

AN:

152040

Hom.:

19500

Cov.:

AF XY:

0.507

AC XY:

37683

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.588

Gnomad4 AMR

AF:

0.486

Gnomad4 ASJ

AF:

0.435

Gnomad4 EAS

AF:

0.490

Gnomad4 SAS

AF:

0.612

Gnomad4 FIN

AF:

0.501

Gnomad4 NFE

AF:

0.454

Gnomad4 OTH

AF:

0.465

Alfa

AF:

0.462

Hom.:

32660

Bravo

AF:

0.501

Asia WGS

AF:

0.580

AC:

2015

AN:

3478

EpiCase

AF:

0.449

EpiControl

AF:

0.442

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.1

DANN

Benign

0.65

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