12-123781140-T-C

Variant names:

Variant summary

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

The NM_001372106.1(DNAH10):c.682T>C(p.Ser228Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 1,613,600 control chromosomes in the GnomAD database, including 325,110 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30974 hom., cov: 30)

Exomes 𝑓: 0.63 ( 294136 hom. )

Consequence

DNAH10
NM_001372106.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.47

Publications

39 publications found

Variant links:

Genes affected

DNAH10 (HGNC:2941): (dynein axonemal heavy chain 10) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. The axonemal dyneins, found in cilia and flagella, are components of the outer and inner dynein arms attached to the peripheral microtubule doublets. DNAH10 is an inner arm dynein heavy chain (Maiti et al., 2000 [PubMed 11175280]).[supplied by OMIM, Mar 2008]

DNAH10 Gene-Disease associations (from GenCC):

spermatogenic failure 56
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

DNAH10 links:

LOC105370044 (HGNC:):

LOC105370044 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=1.1367255E-6).

BP6

Variant 12-123781140-T-C is Benign according to our data. Variant chr12-123781140-T-C is described in ClinVar as Benign. ClinVar VariationId is 402611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH10	NM_001372106.1 link	c.682T>C	p.Ser228Pro	missense_variant	Exon 6 of 79	ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH10	ENST00000673944.1 link	c.682T>C	p.Ser228Pro	missense_variant	Exon 6 of 79		NM_001372106.1	ENSP00000501095.1

Frequencies

GnomAD3 genomes

AF:

0.634

AC:

96171

AN:

151764

Hom.:

30940

Cov.:

show subpopulations

Gnomad AFR

AF:

0.565

Gnomad AMI

AF:

0.593

Gnomad AMR

AF:

0.692

Gnomad ASJ

AF:

0.685

Gnomad EAS

AF:

0.945

Gnomad SAS

AF:

0.702

Gnomad FIN

AF:

0.670

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.626

Gnomad OTH

AF:

0.644

GnomAD2 exomes

AF:

0.667

AC:

167460

AN:

251206

AF XY:

0.666

show subpopulations

Gnomad AFR exome

AF:

0.556

Gnomad AMR exome

AF:

0.696

Gnomad ASJ exome

AF:

0.684

Gnomad EAS exome

AF:

0.949

Gnomad FIN exome

AF:

0.659

Gnomad NFE exome

AF:

0.626

Gnomad OTH exome

AF:

0.652

GnomAD4 exome

AF:

0.631

AC:

922399

AN:

1461720

Hom.:

294136

Cov.:

AF XY:

0.633

AC XY:

460440

AN XY:

727162

show subpopulations

African (AFR)

AF:

0.551

AC:

18438

AN:

33476

American (AMR)

AF:

0.698

AC:

31208

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.686

AC:

17916

AN:

26130

East Asian (EAS)

AF:

0.950

AC:

37710

AN:

39698

South Asian (SAS)

AF:

0.671

AC:

57872

AN:

86250

European-Finnish (FIN)

AF:

0.667

AC:

35617

AN:

53408

Middle Eastern (MID)

AF:

0.592

AC:

3414

AN:

5768

European-Non Finnish (NFE)

AF:

0.613

AC:

681331

AN:

1111886

Other (OTH)

AF:

0.644

AC:

38893

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

18837

37675

56512

75350

94187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18452

36904

55356

73808

92260

<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:

0.634

AC:

96251

AN:

151880

Hom.:

30974

Cov.:

AF XY:

0.640

AC XY:

47528

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.565

AC:

23374

AN:

41362

American (AMR)

AF:

0.693

AC:

10572

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.685

AC:

2380

AN:

3472

East Asian (EAS)

AF:

0.945

AC:

4885

AN:

5172

South Asian (SAS)

AF:

0.703

AC:

3375

AN:

4804

European-Finnish (FIN)

AF:

0.670

AC:

7062

AN:

10544

Middle Eastern (MID)

AF:

0.626

AC:

184

AN:

294

European-Non Finnish (NFE)

AF:

0.626

AC:

42515

AN:

67952

Other (OTH)

AF:

0.648

AC:

1363

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1718

3435

5153

6870

8588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

790

1580

2370

3160

3950

<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:

0.636

Hom.:

94442

Bravo

AF:

0.631

TwinsUK

AF:

0.612

AC:

2268

ESP6500AA

AF:

0.560

AC:

2468

ESP6500EA

AF:

0.630

AC:

5418

ExAC

AF:

0.663

AC:

80462

Asia WGS

AF:

0.808

AC:

2808

AN:

3478

EpiCase

AF:

0.622

EpiControl

AF:

0.630

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

Apr 19, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 30389748, 31178129)

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.062

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.0

.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

LIST_S2

Benign

0.33

T;T

MetaRNN

Benign

0.0000011

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N

PhyloP100

-1.5

PrimateAI

Benign

0.34

PROVEAN

Benign

0.0

.;.

Sift

Pathogenic

0.0

.;.

Sift4G

Pathogenic

0.0

.;.

Vest4

0.0

ClinPred

0.026

GERP RS

-11

Varity_R

0.064

gMVP

0.23

Mutation Taster

=91/9

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

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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