Variant 16-21067372-T-G 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.3291A>C(p.Ala1097Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,613,456 control chromosomes in the GnomAD database, including 147,696 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13664 hom., cov: 31)

Exomes 𝑓: 0.42 ( 134032 hom. )

Consequence

DNAH3
NM_001347886.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.251

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=-0.7).

BP6

Variant 16-21067372-T-G is Benign according to our data. Variant chr16-21067372-T-G is described in ClinVar as [Benign]. Clinvar id is 402724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.251 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.662 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.3291A>C	p.Ala1097Ala	synonymous_variant	24/62	ENST00000698260.1	NP_001334815.1	Q8TD57A0A8V8TLI9B4E1S1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAH3	ENST00000698260.1 linkuse as main transcript	c.3291A>C	p.Ala1097Ala	synonymous_variant	24/62		NM_001347886.2	ENSP00000513632.1	A0A8V8TLI9
DNAH3	ENST00000261383.3 linkuse as main transcript	c.3429A>C	p.Ala1143Ala	synonymous_variant	24/62	1		ENSP00000261383.3	Q8TD57-1
DNAH3	ENST00000685858.1 linkuse as main transcript	c.3471A>C	p.Ala1157Ala	synonymous_variant	24/62			ENSP00000508756.1	A0A8I5KSE2

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63321

AN:

151866

Hom.:

13647

Cov.:

show subpopulations

Gnomad AFR

AF:

0.364

Gnomad AMI

AF:

0.425

Gnomad AMR

AF:

0.425

Gnomad ASJ

AF:

0.445

Gnomad EAS

AF:

0.680

Gnomad SAS

AF:

0.426

Gnomad FIN

AF:

0.476

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.409

GnomAD3 exomes

AF:

0.445

AC:

111818

AN:

251150

Hom.:

25838

AF XY:

0.444

AC XY:

60271

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.366

Gnomad AMR exome

AF:

0.485

Gnomad ASJ exome

AF:

0.444

Gnomad EAS exome

AF:

0.665

Gnomad SAS exome

AF:

0.445

Gnomad FIN exome

AF:

0.463

Gnomad NFE exome

AF:

0.406

Gnomad OTH exome

AF:

0.433

GnomAD4 exome

AF:

0.424

AC:

619363

AN:

1461470

Hom.:

134032

Cov.:

AF XY:

0.424

AC XY:

308309

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.365

Gnomad4 AMR exome

AF:

0.477

Gnomad4 ASJ exome

AF:

0.442

Gnomad4 EAS exome

AF:

0.708

Gnomad4 SAS exome

AF:

0.451

Gnomad4 FIN exome

AF:

0.457

Gnomad4 NFE exome

AF:

0.409

Gnomad4 OTH exome

AF:

0.427

GnomAD4 genome

AF:

0.417

AC:

63375

AN:

151986

Hom.:

13664

Cov.:

AF XY:

0.420

AC XY:

31191

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.364

Gnomad4 AMR

AF:

0.425

Gnomad4 ASJ

AF:

0.445

Gnomad4 EAS

AF:

0.681

Gnomad4 SAS

AF:

0.426

Gnomad4 FIN

AF:

0.476

Gnomad4 NFE

AF:

0.416

Gnomad4 OTH

AF:

0.405

Alfa

AF:

0.410

Hom.:

25889

Bravo

AF:

0.424

EpiCase

AF:

0.404

EpiControl

AF:

0.403

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

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.8

DANN

Benign

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