rs61735917

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001372106.1(DNAH10):c.9540C>T(p.Asp3180Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.005 in 1,604,774 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0087 ( 10 hom., cov: 33)

Exomes 𝑓: 0.0046 ( 24 hom. )

Consequence

DNAH10
NM_001372106.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.412

Publications

3 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 12-123898714-C-T is Benign according to our data. Variant chr12-123898714-C-T is described in ClinVar as Benign. ClinVar VariationId is 402620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.412 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0087 (1325/152360) while in subpopulation AFR AF = 0.0193 (802/41584). AF 95% confidence interval is 0.0182. There are 10 homozygotes in GnomAd4. There are 626 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH10	NM_001372106.1 link	c.9540C>T	p.Asp3180Asp	synonymous_variant	Exon 56 of 79	ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
DNAH10	ENST00000673944.1 link	c.9540C>T	p.Asp3180Asp	synonymous_variant	Exon 56 of 79		NM_001372106.1	ENSP00000501095.1
DNAH10	ENST00000409039.8 link	c.9369C>T	p.Asp3123Asp	synonymous_variant	Exon 55 of 78	5		ENSP00000386770.4
DNAH10	ENST00000638045.1 link	c.9186C>T	p.Asp3062Asp	synonymous_variant	Exon 55 of 78	5		ENSP00000489675.1

Frequencies

GnomAD3 genomes

AF:

0.00870

AC:

1324

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00876

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00555

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00445

Gnomad OTH

AF:

0.00907

GnomAD2 exomes

AF:

0.00516

AC:

1189

AN:

230510

AF XY:

0.00471

show subpopulations

Gnomad AFR exome

AF:

0.0200

Gnomad AMR exome

AF:

0.00737

Gnomad ASJ exome

AF:

0.00145

Gnomad EAS exome

AF:

0.0000599

Gnomad FIN exome

AF:

0.00494

Gnomad NFE exome

AF:

0.00513

Gnomad OTH exome

AF:

0.00423

GnomAD4 exome

AF:

0.00461

AC:

6699

AN:

1452414

Hom.:

Cov.:

AF XY:

0.00450

AC XY:

3248

AN XY:

721432

show subpopulations

African (AFR)

AF:

0.0183

AC:

610

AN:

33318

American (AMR)

AF:

0.00816

AC:

354

AN:

43392

Ashkenazi Jewish (ASJ)

AF:

0.00170

AC:

AN:

25902

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39298

South Asian (SAS)

AF:

0.000143

AC:

AN:

84114

European-Finnish (FIN)

AF:

0.00477

AC:

251

AN:

52672

Middle Eastern (MID)

AF:

0.00417

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00461

AC:

5110

AN:

1107942

Other (OTH)

AF:

0.00488

AC:

293

AN:

60024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

407

813

1220

1626

2033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

392

588

784

980

<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:

0.00870

AC:

1325

AN:

152360

Hom.:

Cov.:

AF XY:

0.00840

AC XY:

626

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.0193

AC:

802

AN:

41584

American (AMR)

AF:

0.00875

AC:

134

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00555

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00445

AC:

303

AN:

68026

Other (OTH)

AF:

0.00898

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

135

203

270

338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00596

Hom.:

Bravo

AF:

0.00985

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 28, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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, silent variant not in splice consensus -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

1.5

(source)

DANN

Benign

0.79

PhyloP100

-0.41

Mutation Taster

=100/0

polymorphism

(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