Variant rs861424 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.3291A>T(p.Ala1097=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00378 in 1,613,756 control chromosomes in the GnomAD database, including 211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. A1097A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.021 ( 120 hom., cov: 31)

Exomes 𝑓: 0.0020 ( 91 hom. )

Consequence

DNAH3
NM_001347886.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 16-21067372-T-A is Benign according to our data. Variant chr16-21067372-T-A is described in ClinVar as [Benign]. Clinvar id is 782410.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.251 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0705 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.3291A>T	p.Ala1097=	synonymous_variant	24/62	ENST00000698260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH3	ENST00000698260.1 linkuse as main transcript	c.3291A>T	p.Ala1097=	synonymous_variant	24/62		NM_001347886.2	P1
DNAH3	ENST00000261383.3 linkuse as main transcript	c.3429A>T	p.Ala1143=	synonymous_variant	24/62	1			Q8TD57-1
DNAH3	ENST00000685858.1 linkuse as main transcript	c.3471A>T	p.Ala1157=	synonymous_variant	24/62

Frequencies

GnomAD3 genomes

AF:

0.0212

AC:

3218

AN:

151924

Hom.:

120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0729

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00997

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00534

AC:

1341

AN:

251150

Hom.:

AF XY:

0.00376

AC XY:

510

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.0713

Gnomad AMR exome

AF:

0.00367

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000247

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00197

AC:

2875

AN:

1461712

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

1249

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0676

Gnomad4 AMR exome

AF:

0.00400

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000129

Gnomad4 OTH exome

AF:

0.00441

GnomAD4 genome

AF:

0.0212

AC:

3219

AN:

152044

Hom.:

120

Cov.:

AF XY:

0.0205

AC XY:

1520

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.0727

Gnomad4 AMR

AF:

0.00996

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.0000804

Hom.:

25889

EpiCase

AF:

0.000218

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.6

DANN

Benign

0.60

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