12-123845764-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_001372106.1(DNAH10):c.5525C>T(p.Thr1842Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,613,898 control chromosomes in the GnomAD database, including 10,189 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 0.082 ( 682 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9507 hom. )

Consequence

DNAH10
NM_001372106.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.60

Publications

17 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:

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=0.0024943054).

BP6

Variant 12-123845764-C-T is Benign according to our data. Variant chr12-123845764-C-T is described in ClinVar as Benign. ClinVar VariationId is 402616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372106.1. 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
	DNAH10	NM_001372106.1	MANE Select	c.5525C>T	p.Thr1842Met	missense	Exon 31 of 79	NP_001359035.1
	DNAH10	NM_207437.3		c.5171C>T	p.Thr1724Met	missense	Exon 30 of 78	NP_997320.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAH10	ENST00000673944.1	MANE Select	c.5525C>T	p.Thr1842Met	missense	Exon 31 of 79	ENSP00000501095.1
DNAH10	ENST00000409039.8	TSL:5	c.5354C>T	p.Thr1785Met	missense	Exon 30 of 78	ENSP00000386770.4
DNAH10	ENST00000638045.1	TSL:5	c.5171C>T	p.Thr1724Met	missense	Exon 30 of 78	ENSP00000489675.1

Frequencies

GnomAD3 genomes

AF:

0.0823

AC:

12510

AN:

152090

Hom.:

681

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0233

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.0928

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0592

Gnomad FIN

AF:

0.0720

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.103

GnomAD2 exomes

AF:

0.0866

AC:

21594

AN:

249236

AF XY:

0.0891

show subpopulations

Gnomad AFR exome

AF:

0.0224

Gnomad AMR exome

AF:

0.0634

Gnomad ASJ exome

AF:

0.126

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.0777

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.109

AC:

159130

AN:

1461690

Hom.:

9507

Cov.:

AF XY:

0.108

AC XY:

78864

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.0240

AC:

805

AN:

33480

American (AMR)

AF:

0.0674

AC:

3014

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

3413

AN:

26136

East Asian (EAS)

AF:

0.000176

AC:

AN:

39700

South Asian (SAS)

AF:

0.0673

AC:

5805

AN:

86258

European-Finnish (FIN)

AF:

0.0856

AC:

4572

AN:

53392

Middle Eastern (MID)

AF:

0.113

AC:

651

AN:

5768

European-Non Finnish (NFE)

AF:

0.121

AC:

134800

AN:

1111860

Other (OTH)

AF:

0.100

AC:

6063

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

9958

19916

29874

39832

49790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4784

9568

14352

19136

23920

<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:

0.0822

AC:

12513

AN:

152208

Hom.:

682

Cov.:

AF XY:

0.0789

AC XY:

5869

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0233

AC:

969

AN:

41538

American (AMR)

AF:

0.0926

AC:

1416

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

435

AN:

3464

East Asian (EAS)

AF:

0.00116

AC:

AN:

5174

South Asian (SAS)

AF:

0.0599

AC:

288

AN:

4812

European-Finnish (FIN)

AF:

0.0720

AC:

764

AN:

10604

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.121

AC:

8211

AN:

68014

Other (OTH)

AF:

0.102

AC:

216

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

592

1184

1776

2368

2960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<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:

0.105

Hom.:

2138

Bravo

AF:

0.0824

TwinsUK

AF:

0.119

AC:

442

ALSPAC

AF:

0.121

AC:

467

ESP6500AA

AF:

0.0235

AC:

ESP6500EA

AF:

0.117

AC:

982

ExAC

AF:

0.0872

AC:

10550

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

EpiCase

AF:

0.126

EpiControl

AF:

0.129

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: MAF

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

0.090

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.0032

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

PhyloP100

2.6

PrimateAI

Benign

0.43

REVEL

Benign

0.071

Polyphen

0.47

MPC

0.16

ClinPred

0.019

GERP RS

4.9

Varity_R

0.027

gMVP

0.37

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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

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