3-57433770-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001366028.2(DNAH12):c.4714G>A(p.Asp1572Asn) variant causes a missense change. The variant allele was found at a frequency of 0.486 in 1,550,106 control chromosomes in the GnomAD database, including 187,650 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 15034 hom., cov: 32)

Exomes 𝑓: 0.49 ( 172616 hom. )

Consequence

DNAH12
NM_001366028.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.07

Publications

17 publications found

Variant links:

Genes affected

DNAH12 (HGNC:2943): (dynein axonemal heavy chain 12) Predicted to enable several functions, including ATP binding activity; dynein intermediate chain binding activity; and dynein light intermediate chain binding activity. Predicted to be involved in microtubule-based movement. Predicted to be located in cilium; cytoplasm; and microtubule. Predicted to be part of dynein complex. [provided by Alliance of Genome Resources, Apr 2022]

DNAH12 Gene-Disease associations (from GenCC):

oligoasthenoteratozoospermia
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

DNAH12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.866323E-4).

BP6

Variant 3-57433770-C-T is Benign according to our data. Variant chr3-57433770-C-T is described in ClinVar as Benign. ClinVar VariationId is 402636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366028.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH12	NM_001366028.2	MANE Select	c.4714G>A	p.Asp1572Asn	missense	Exon 31 of 74	NP_001352957.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH12	ENST00000495027.6	TSL:5 MANE Select	c.4714G>A	p.Asp1572Asn	missense	Exon 31 of 74	ENSP00000418137.2
	DNAH12	ENST00000351747.6	TSL:5	c.4645G>A	p.Asp1549Asn	missense	Exon 31 of 59	ENSP00000295937.3

Frequencies

GnomAD3 genomes

AF:

0.420

AC:

63735

AN:

151884

Hom.:

15034

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.624

Gnomad AMR

AF:

0.482

Gnomad ASJ

AF:

0.578

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.580

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.498

Gnomad OTH

AF:

0.455

GnomAD2 exomes

AF:

0.494

AC:

75600

AN:

152926

AF XY:

0.503

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.470

Gnomad ASJ exome

AF:

0.585

Gnomad EAS exome

AF:

0.412

Gnomad FIN exome

AF:

0.578

Gnomad NFE exome

AF:

0.501

Gnomad OTH exome

AF:

0.504

GnomAD4 exome

AF:

0.493

AC:

688985

AN:

1398106

Hom.:

172616

Cov.:

AF XY:

0.497

AC XY:

342378

AN XY:

689498

show subpopulations

African (AFR)

AF:

0.177

AC:

5587

AN:

31564

American (AMR)

AF:

0.473

AC:

16806

AN:

35512

Ashkenazi Jewish (ASJ)

AF:

0.584

AC:

14691

AN:

25142

East Asian (EAS)

AF:

0.442

AC:

15775

AN:

35702

South Asian (SAS)

AF:

0.563

AC:

44438

AN:

78886

European-Finnish (FIN)

AF:

0.569

AC:

27944

AN:

49108

Middle Eastern (MID)

AF:

0.566

AC:

3223

AN:

5690

European-Non Finnish (NFE)

AF:

0.493

AC:

531948

AN:

1078540

Other (OTH)

AF:

0.493

AC:

28573

AN:

57962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

18113

36226

54339

72452

90565

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15622

31244

46866

62488

78110

<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:

0.419

AC:

63737

AN:

152000

Hom.:

15034

Cov.:

AF XY:

0.428

AC XY:

31786

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.188

AC:

7819

AN:

41488

American (AMR)

AF:

0.481

AC:

7350

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.578

AC:

2000

AN:

3462

East Asian (EAS)

AF:

0.421

AC:

2175

AN:

5170

South Asian (SAS)

AF:

0.570

AC:

2743

AN:

4810

European-Finnish (FIN)

AF:

0.580

AC:

6117

AN:

10546

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.498

AC:

33863

AN:

67944

Other (OTH)

AF:

0.456

AC:

962

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1751

3502

5252

7003

8754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

596

1192

1788

2384

2980

<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:

0.477

Hom.:

36822

Bravo

AF:

0.397

TwinsUK

AF:

0.499

AC:

1850

ALSPAC

AF:

0.486

AC:

1874

ESP6500AA

AF:

0.184

AC:

254

ESP6500EA

AF:

0.497

AC:

1582

ExAC

AF:

0.480

AC:

10186

Asia WGS

AF:

0.512

AC:

1782

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.022

Eigen

Benign

0.16

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.00079

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.2

PhyloP100

6.1

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.3

REVEL

Benign

0.19

Sift

Benign

0.37

Polyphen

0.99

Vest4

0.15

ClinPred

0.051

GERP RS

4.9

Varity_R

0.10

Mutation Taster

=88/12

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over