3-57301848-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.11281G>A(p.Gly3761Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 1,551,332 control chromosomes in the GnomAD database, including 304,603 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 0.61 ( 28517 hom., cov: 31)

Exomes 𝑓: 0.62 ( 276086 hom. )

Consequence

DNAH12
NM_001366028.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.479

Publications

26 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=4.1477865E-6).

BP6

Variant 3-57301848-C-T is Benign according to our data. Variant chr3-57301848-C-T is described in ClinVar as Benign. ClinVar VariationId is 402630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH12	NM_001366028.2 link	c.11281G>A	p.Gly3761Ser	missense_variant	Exon 70 of 74	ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
DNAH12	ENST00000495027.6 link	c.11281G>A	p.Gly3761Ser	missense_variant	Exon 70 of 74	5	NM_001366028.2	ENSP00000418137.2
DNAH12	ENST00000351747.6 link	c.8677G>A	p.Gly2893Ser	missense_variant	Exon 55 of 59	5		ENSP00000295937.3
DNAH12	ENST00000466540.2 link	c.1618G>A	p.Gly540Ser	missense_variant	Exon 11 of 15	5		ENSP00000420359.2
DNAH12	ENST00000494758.5 link	n.96-4864G>A		intron_variant	Intron 1 of 4	2		ENSP00000420717.1

Frequencies

GnomAD3 genomes

AF:

0.605

AC:

91889

AN:

151810

Hom.:

28492

Cov.:

show subpopulations

Gnomad AFR

AF:

0.490

Gnomad AMI

AF:

0.620

Gnomad AMR

AF:

0.718

Gnomad ASJ

AF:

0.557

Gnomad EAS

AF:

0.924

Gnomad SAS

AF:

0.643

Gnomad FIN

AF:

0.695

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.612

Gnomad OTH

AF:

0.599

GnomAD2 exomes

AF:

0.660

AC:

103557

AN:

156914

AF XY:

0.655

show subpopulations

Gnomad AFR exome

AF:

0.486

Gnomad AMR exome

AF:

0.766

Gnomad ASJ exome

AF:

0.566

Gnomad EAS exome

AF:

0.939

Gnomad FIN exome

AF:

0.694

Gnomad NFE exome

AF:

0.611

Gnomad OTH exome

AF:

0.625

GnomAD4 exome

AF:

0.624

AC:

873762

AN:

1399404

Hom.:

276086

Cov.:

AF XY:

0.624

AC XY:

430442

AN XY:

690200

show subpopulations

African (AFR)

AF:

0.480

AC:

15162

AN:

31598

American (AMR)

AF:

0.754

AC:

26932

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.563

AC:

14164

AN:

25180

East Asian (EAS)

AF:

0.913

AC:

32638

AN:

35730

South Asian (SAS)

AF:

0.622

AC:

49281

AN:

79236

European-Finnish (FIN)

AF:

0.692

AC:

34127

AN:

49290

Middle Eastern (MID)

AF:

0.569

AC:

3242

AN:

5696

European-Non Finnish (NFE)

AF:

0.614

AC:

661989

AN:

1078962

Other (OTH)

AF:

0.625

AC:

36227

AN:

58008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

20081

40162

60242

80323

100404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18074

36148

54222

72296

90370

<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:

0.605

AC:

91965

AN:

151928

Hom.:

28517

Cov.:

AF XY:

0.611

AC XY:

45349

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.490

AC:

20284

AN:

41394

American (AMR)

AF:

0.718

AC:

10968

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.557

AC:

1928

AN:

3464

East Asian (EAS)

AF:

0.924

AC:

4784

AN:

5180

South Asian (SAS)

AF:

0.644

AC:

3093

AN:

4802

European-Finnish (FIN)

AF:

0.695

AC:

7333

AN:

10554

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.612

AC:

41580

AN:

67946

Other (OTH)

AF:

0.604

AC:

1273

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1802

3603

5405

7206

9008

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.613

Hom.:

73486

Bravo

AF:

0.603

TwinsUK

AF:

0.618

AC:

2293

ALSPAC

AF:

0.614

AC:

2367

ESP6500AA

AF:

0.499

AC:

691

ESP6500EA

AF:

0.611

AC:

1943

ExAC

AF:

0.602

AC:

14725

Asia WGS

AF:

0.765

AC:

2657

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.056

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.0010

T;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.68

T;T

MetaRNN

Benign

0.0000041

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.060

.;N

PhyloP100

-0.48

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.31

.;N

REVEL

Benign

0.15

Sift

Benign

1.0

.;T

Polyphen

0.12

.;B

Vest4

0.050

ClinPred

0.0013

GERP RS

2.3

Varity_R

0.060

Mutation Taster

=89/11

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

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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