dbSNP rs861424: DNAH3:p.Ala1097Ala (chr16-21067372-T-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001347886.2(DNAH3):c.3291A>T(p.Ala1097Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00378 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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.251

Publications

20 publications found

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 Gene-Disease associations (from GenCC):

male infertility
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

DNAH3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 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 VariationId is 782410.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 (AFR) allele frequency at 95% confidence interval = 0.0705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH3	NM_001347886.2 link	c.3291A>T	p.Ala1097Ala	synonymous_variant	Exon 24 of 62	ENST00000698260.1	NP_001334815.1	Q8TD57A0A8V8TLI9B4E1S1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH3	ENST00000698260.1 link	c.3291A>T	p.Ala1097Ala	synonymous_variant	Exon 24 of 62		NM_001347886.2	ENSP00000513632.1	A0A8V8TLI9
DNAH3	ENST00000261383.3 link	c.3429A>T	p.Ala1143Ala	synonymous_variant	Exon 24 of 62	1		ENSP00000261383.3	Q8TD57-1
DNAH3	ENST00000685858.1 link	c.3471A>T	p.Ala1157Ala	synonymous_variant	Exon 24 of 62			ENSP00000508756.1	A0A8I5KSE2

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

GnomAD2 exomes

AF:

0.00534

AC:

1341

AN:

251150

AF XY:

0.00376

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 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

African (AFR)

AF:

0.0676

AC:

2264

AN:

33472

American (AMR)

AF:

0.00400

AC:

179

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000116

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000129

AC:

143

AN:

1111882

Other (OTH)

AF:

0.00441

AC:

266

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

138

276

414

552

690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0212

AC:

3219

AN:

152044

Hom.:

120

Cov.:

AF XY:

0.0205

AC XY:

1520

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.0727

AC:

3015

AN:

41492

American (AMR)

AF:

0.00996

AC:

152

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5130

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

67986

Other (OTH)

AF:

0.0151

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

138

275

413

550

688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000583

Hom.:

35694

EpiCase

AF:

0.000218

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.6

(source)

DANN

Benign

0.60

PhyloP100

0.25

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over