chr3-52396510-G-A

Variant names:

Variant summary

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

The NM_015512.5(DNAH1):c.11402G>A(p.Gly3801Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,610,062 control chromosomes in the GnomAD database, including 33,361 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 0.16 ( 2538 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30823 hom. )

Consequence

DNAH1
NM_015512.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.05

Publications

32 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051918626).

BP6

Variant 3-52396510-G-A is Benign according to our data. Variant chr3-52396510-G-A is described in ClinVar as Benign. ClinVar VariationId is 402604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5 link	c.11402G>A	p.Gly3801Asp	missense_variant	Exon 71 of 78	ENST00000420323.7	NP_056327.4	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006129.2 link	c.11471G>A	p.Gly3824Asp	missense_variant	Exon 73 of 80		XP_016861618.1
DNAH1	XM_017006130.2 link	c.11402G>A	p.Gly3801Asp	missense_variant	Exon 72 of 79		XP_016861619.1	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006131.2 link	c.11345G>A	p.Gly3782Asp	missense_variant	Exon 72 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH1	ENST00000420323.7 link	c.11402G>A	p.Gly3801Asp	missense_variant	Exon 71 of 78	1	NM_015512.5	ENSP00000401514.2	Q9P2D7-4
DNAH1	ENST00000486752.5 link	n.11859G>A		non_coding_transcript_exon_variant	Exon 70 of 77	2
DNAH1	ENST00000488988.5 link	n.3188G>A		non_coding_transcript_exon_variant	Exon 18 of 25	2
DNAH1	ENST00000490713.5 link	n.2102G>A		non_coding_transcript_exon_variant	Exon 14 of 20	5		ENSP00000419071.1	H7C563

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24503

AN:

151994

Hom.:

2539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0469

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.173

GnomAD2 exomes

AF:

0.193

AC:

46753

AN:

242176

AF XY:

0.200

show subpopulations

Gnomad AFR exome

AF:

0.0445

Gnomad AMR exome

AF:

0.0935

Gnomad ASJ exome

AF:

0.225

Gnomad EAS exome

AF:

0.270

Gnomad FIN exome

AF:

0.260

Gnomad NFE exome

AF:

0.204

Gnomad OTH exome

AF:

0.209

GnomAD4 exome

AF:

0.201

AC:

293354

AN:

1457950

Hom.:

30823

Cov.:

AF XY:

0.204

AC XY:

147697

AN XY:

724932

show subpopulations

African (AFR)

AF:

0.0371

AC:

1240

AN:

33428

American (AMR)

AF:

0.0976

AC:

4313

AN:

44174

Ashkenazi Jewish (ASJ)

AF:

0.222

AC:

5786

AN:

26064

East Asian (EAS)

AF:

0.200

AC:

7892

AN:

39514

South Asian (SAS)

AF:

0.235

AC:

20179

AN:

85800

European-Finnish (FIN)

AF:

0.260

AC:

13733

AN:

52860

Middle Eastern (MID)

AF:

0.223

AC:

1286

AN:

5766

European-Non Finnish (NFE)

AF:

0.204

AC:

226450

AN:

1110108

Other (OTH)

AF:

0.207

AC:

12475

AN:

60236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

14470

28940

43410

57880

72350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7880

15760

23640

31520

39400

<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:

0.161

AC:

24499

AN:

152112

Hom.:

2538

Cov.:

AF XY:

0.165

AC XY:

12280

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0469

AC:

1946

AN:

41534

American (AMR)

AF:

0.140

AC:

2136

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.220

AC:

764

AN:

3472

East Asian (EAS)

AF:

0.269

AC:

1388

AN:

5154

South Asian (SAS)

AF:

0.228

AC:

1100

AN:

4816

European-Finnish (FIN)

AF:

0.254

AC:

2686

AN:

10564

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.203

AC:

13810

AN:

67976

Other (OTH)

AF:

0.171

AC:

361

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

978

1956

2933

3911

4889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<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:

0.188

Hom.:

10034

Bravo

AF:

0.147

TwinsUK

AF:

0.210

AC:

778

ALSPAC

AF:

0.201

AC:

773

ESP6500AA

AF:

0.0478

AC:

203

ESP6500EA

AF:

0.189

AC:

1603

ExAC

AF:

0.191

AC:

23105

Asia WGS

AF:

0.209

AC:

728

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 09, 2018

GeneDx

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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 -

Ciliary dyskinesia, primary, 37

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spermatogenic failure 18

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.63

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.74

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0052

MetaSVM

Benign

-0.91

PhyloP100

2.1

PrimateAI

Benign

0.46

PROVEAN

Benign

0.51

REVEL

Benign

0.041

Sift

Benign

0.69

Sift4G

Benign

1.0

Vest4

0.083

MPC

0.16

ClinPred

0.00093

GERP RS

2.4

gMVP

0.41

Mutation Taster

=98/2

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