3-57489624-T-G

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.1399A>C(p.Thr467Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,540,110 control chromosomes in the GnomAD database, including 353,121 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34243 hom., cov: 30)

Exomes 𝑓: 0.68 ( 318878 hom. )

Consequence

DNAH12
NM_001366028.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.87

Publications

23 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=6.864867E-7).

BP6

Variant 3-57489624-T-G is Benign according to our data. Variant chr3-57489624-T-G is described in ClinVar as Benign. ClinVar VariationId is 402642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH12	NM_001366028.2 link	c.1399A>C	p.Thr467Pro	missense_variant	Exon 12 of 74	ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
DNAH12	ENST00000495027.6 link	c.1399A>C	p.Thr467Pro	missense_variant	Exon 12 of 74	5	NM_001366028.2	ENSP00000418137.2
DNAH12	ENST00000351747.6 link	c.1399A>C	p.Thr467Pro	missense_variant	Exon 12 of 59	5		ENSP00000295937.3
DNAH12	ENST00000389536.8 link	c.1399A>C	p.Thr467Pro	missense_variant	Exon 12 of 17	5		ENSP00000374187.4

Frequencies

GnomAD3 genomes

AF:

0.670

AC:

101478

AN:

151496

Hom.:

34237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.645

Gnomad AMI

AF:

0.832

Gnomad AMR

AF:

0.637

Gnomad ASJ

AF:

0.790

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.751

Gnomad FIN

AF:

0.723

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.683

Gnomad OTH

AF:

0.677

GnomAD2 exomes

AF:

0.672

AC:

97268

AN:

144648

AF XY:

0.681

show subpopulations

Gnomad AFR exome

AF:

0.639

Gnomad AMR exome

AF:

0.587

Gnomad ASJ exome

AF:

0.794

Gnomad EAS exome

AF:

0.465

Gnomad FIN exome

AF:

0.727

Gnomad NFE exome

AF:

0.679

Gnomad OTH exome

AF:

0.673

GnomAD4 exome

AF:

0.676

AC:

938852

AN:

1388496

Hom.:

318878

Cov.:

AF XY:

0.679

AC XY:

465001

AN XY:

684538

show subpopulations

African (AFR)

AF:

0.645

AC:

19895

AN:

30856

American (AMR)

AF:

0.597

AC:

19823

AN:

33182

Ashkenazi Jewish (ASJ)

AF:

0.795

AC:

19876

AN:

24990

East Asian (EAS)

AF:

0.519

AC:

18156

AN:

34954

South Asian (SAS)

AF:

0.759

AC:

58050

AN:

76520

European-Finnish (FIN)

AF:

0.721

AC:

35464

AN:

49178

Middle Eastern (MID)

AF:

0.747

AC:

4243

AN:

5680

European-Non Finnish (NFE)

AF:

0.673

AC:

724258

AN:

1075566

Other (OTH)

AF:

0.679

AC:

39087

AN:

57570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

16008

32015

48023

64030

80038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18938

37876

56814

75752

94690

<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:

0.670

AC:

101531

AN:

151614

Hom.:

34243

Cov.:

AF XY:

0.673

AC XY:

49833

AN XY:

74090

show subpopulations

African (AFR)

AF:

0.645

AC:

26614

AN:

41258

American (AMR)

AF:

0.636

AC:

9672

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.790

AC:

2740

AN:

3470

East Asian (EAS)

AF:

0.489

AC:

2517

AN:

5150

South Asian (SAS)

AF:

0.751

AC:

3607

AN:

4802

European-Finnish (FIN)

AF:

0.723

AC:

7589

AN:

10498

Middle Eastern (MID)

AF:

0.701

AC:

206

AN:

294

European-Non Finnish (NFE)

AF:

0.683

AC:

46406

AN:

67920

Other (OTH)

AF:

0.675

AC:

1421

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1680

3360

5040

6720

8400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

802

1604

2406

3208

4010

<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:

0.676

Hom.:

86419

Bravo

AF:

0.658

TwinsUK

AF:

0.688

AC:

2551

ALSPAC

AF:

0.668

AC:

2573

ESP6500AA

AF:

0.629

AC:

871

ESP6500EA

AF:

0.686

AC:

2182

ExAC

AF:

0.700

AC:

16371

Asia WGS

AF:

0.657

AC:

2280

AN:

3472

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.038

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0072

T;T;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.071

T;T;T

MetaRNN

Benign

6.9e-7

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.7

.;N;.

PhyloP100

2.9

PrimateAI

Benign

0.43

PROVEAN

Benign

2.2

N;N;N

REVEL

Benign

0.077

Sift

Benign

0.46

T;T;T

Sift4G

Benign

1.0

.;.;T

Polyphen

0.0

.;B;.

Vest4

0.077

ClinPred

0.0060

GERP RS

5.4

Varity_R

0.18

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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