NM_015512.5:c.10881C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_015512.5(DNAH1):c.10881C>A(p.Val3627Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,612,930 control chromosomes in the GnomAD database, including 10,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.077 ( 613 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10034 hom. )

Consequence

DNAH1
NM_015512.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.81

Publications

19 publications found

Variant links:

Genes affected

DNAH1 (HGNC:2940): (dynein axonemal heavy chain 1) This gene encodes an inner dynein arm heavy chain that provides structural support between the radial spokes and the outer doublet of the sperm tail. Naturally occurring mutations in this gene are associated with primary ciliary dyskinesia and multiple morphological anomalies of the flagella that result in asthenozoospermia and male infertility. Mice with a homozygous knockout of the orthologous gene are viable but have reduced sperm motility and are infertile. [provided by RefSeq, Feb 2017]

DNAH1 Gene-Disease associations (from GenCC):

spermatogenic failure 18
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
ciliary dyskinesia, primary, 37
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
non-syndromic male infertility due to sperm motility disorder
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DNAH1 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=-0.25).

BP6

Variant 3-52394972-C-A is Benign according to our data. Variant chr3-52394972-C-A is described in ClinVar as Benign. ClinVar VariationId is 402603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.81 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5 link	c.10881C>A	p.Val3627Val	synonymous_variant	Exon 68 of 78	ENST00000420323.7	NP_056327.4	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006129.2 link	c.10950C>A	p.Val3650Val	synonymous_variant	Exon 70 of 80		XP_016861618.1
DNAH1	XM_017006130.2 link	c.10881C>A	p.Val3627Val	synonymous_variant	Exon 69 of 79		XP_016861619.1	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006131.2 link	c.10824C>A	p.Val3608Val	synonymous_variant	Exon 69 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7 link	c.10881C>A	p.Val3627Val	synonymous_variant	Exon 68 of 78	1	NM_015512.5	ENSP00000401514.2		Q9P2D7-4

Frequencies

GnomAD3 genomes

AF:

0.0770

AC:

11716

AN:

152194

Hom.:

614

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0191

Gnomad AMI

AF:

0.0716

Gnomad AMR

AF:

0.0731

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0650

Gnomad FIN

AF:

0.0522

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.101

GnomAD2 exomes

AF:

0.0832

AC:

20532

AN:

246738

AF XY:

0.0845

show subpopulations

Gnomad AFR exome

AF:

0.0171

Gnomad AMR exome

AF:

0.0630

Gnomad ASJ exome

AF:

0.119

Gnomad EAS exome

AF:

0.000223

Gnomad FIN exome

AF:

0.0561

Gnomad NFE exome

AF:

0.117

Gnomad OTH exome

AF:

0.0924

GnomAD4 exome

AF:

0.111

AC:

162647

AN:

1460618

Hom.:

10034

Cov.:

AF XY:

0.110

AC XY:

79981

AN XY:

726502

show subpopulations

African (AFR)

AF:

0.0183

AC:

612

AN:

33474

American (AMR)

AF:

0.0658

AC:

2932

AN:

44568

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

3109

AN:

26112

East Asian (EAS)

AF:

0.000302

AC:

AN:

39686

South Asian (SAS)

AF:

0.0737

AC:

6337

AN:

85998

European-Finnish (FIN)

AF:

0.0588

AC:

3136

AN:

53288

Middle Eastern (MID)

AF:

0.0987

AC:

569

AN:

5766

European-Non Finnish (NFE)

AF:

0.126

AC:

139629

AN:

1111396

Other (OTH)

AF:

0.105

AC:

6311

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

8321

16643

24964

33286

41607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5010

10020

15030

20040

25050

<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:

0.0769

AC:

11712

AN:

152312

Hom.:

613

Cov.:

AF XY:

0.0741

AC XY:

5522

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0190

AC:

791

AN:

41582

American (AMR)

AF:

0.0730

AC:

1117

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

436

AN:

3472

East Asian (EAS)

AF:

0.000770

AC:

AN:

5192

South Asian (SAS)

AF:

0.0657

AC:

317

AN:

4828

European-Finnish (FIN)

AF:

0.0522

AC:

554

AN:

10622

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.120

AC:

8184

AN:

68000

Other (OTH)

AF:

0.0998

AC:

211

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

567

1134

1701

2268

2835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

288

432

576

720

<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:

0.100

Hom.:

1406

Bravo

AF:

0.0756

Asia WGS

AF:

0.0260

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

- -

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 -

Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

1.7

(source)

DANN

Benign

0.74

PhyloP100

-1.8

Mutation Taster

=100/0

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