rs75513160

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.10305G>A(p.Thr3435Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,597,196 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 64 hom., cov: 29)

Exomes 𝑓: 0.0019 ( 66 hom. )

Consequence

DNAH1
NM_015512.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.32

Publications

3 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=-0.43).

BP6

Variant 3-52392856-G-A is Benign according to our data. Variant chr3-52392856-G-A is described in ClinVar as Benign. ClinVar VariationId is 478377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.32 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5 link	c.10305G>A	p.Thr3435Thr	synonymous_variant	Exon 65 of 78	ENST00000420323.7	NP_056327.4	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006129.2 link	c.10374G>A	p.Thr3458Thr	synonymous_variant	Exon 67 of 80		XP_016861618.1
DNAH1	XM_017006130.2 link	c.10305G>A	p.Thr3435Thr	synonymous_variant	Exon 66 of 79		XP_016861619.1	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006131.2 link	c.10248G>A	p.Thr3416Thr	synonymous_variant	Exon 66 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH1	ENST00000420323.7 link	c.10305G>A	p.Thr3435Thr	synonymous_variant	Exon 65 of 78	1	NM_015512.5	ENSP00000401514.2	Q9P2D7-4
DNAH1	ENST00000486752.5 link	n.10762G>A		non_coding_transcript_exon_variant	Exon 64 of 77	2
DNAH1	ENST00000488988.5 link	n.2091G>A		non_coding_transcript_exon_variant	Exon 12 of 25	2
DNAH1	ENST00000490713.5 link	n.1005G>A		non_coding_transcript_exon_variant	Exon 8 of 20	5		ENSP00000419071.1	H7C563

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2205

AN:

143144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0544

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000439

Gnomad FIN

AF:

0.000226

Gnomad MID

AF:

0.00680

Gnomad NFE

AF:

0.000703

Gnomad OTH

AF:

0.0107

GnomAD2 exomes

AF:

0.00391

AC:

969

AN:

247530

AF XY:

0.00282

show subpopulations

Gnomad AFR exome

AF:

0.0530

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000655

Gnomad OTH exome

AF:

0.00282

GnomAD4 exome

AF:

0.00189

AC:

2742

AN:

1453972

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

1190

AN XY:

721488

show subpopulations

African (AFR)

AF:

0.0564

AC:

1881

AN:

33370

American (AMR)

AF:

0.00202

AC:

AN:

44604

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26074

East Asian (EAS)

AF:

0.00

AC:

AN:

39362

South Asian (SAS)

AF:

0.000256

AC:

AN:

86092

European-Finnish (FIN)

AF:

0.000320

AC:

AN:

53174

Middle Eastern (MID)

AF:

0.00453

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.000427

AC:

472

AN:

1105592

Other (OTH)

AF:

0.00390

AC:

234

AN:

59962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

130

261

391

522

652

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<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:

0.0154

AC:

2211

AN:

143224

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1021

AN XY:

68876

show subpopulations

African (AFR)

AF:

0.0544

AC:

2084

AN:

38276

American (AMR)

AF:

0.00399

AC:

AN:

13290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

4828

South Asian (SAS)

AF:

0.000441

AC:

AN:

4538

European-Finnish (FIN)

AF:

0.000226

AC:

AN:

8862

Middle Eastern (MID)

AF:

0.00725

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.000703

AC:

AN:

66826

Other (OTH)

AF:

0.0106

AC:

AN:

1974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

178

266

355

444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00646

Hom.:

Bravo

AF:

0.0175

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 09, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 22, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

- -

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

Benign:1

Jan 24, 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

-0.43

CADD

Benign

4.8

(source)

DANN

Benign

0.72

PhyloP100

-1.3

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