3-52392868-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015512.5(DNAH1):c.10317C>T(p.Ile3439Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 1,608,620 control chromosomes in the GnomAD database, including 1,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 141 hom., cov: 30)

Exomes 𝑓: 0.045 ( 1646 hom. )

Consequence

DNAH1
NM_015512.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.67

Publications

12 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 (BayesDel_noAF=-0.61).

BP6

Variant 3-52392868-C-T is Benign according to our data. Variant chr3-52392868-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 478382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0381 (5666/148804) while in subpopulation NFE AF = 0.0494 (3323/67324). AF 95% confidence interval is 0.048. There are 141 homozygotes in GnomAd4. There are 2595 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 141 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
DNAH1	NM_015512.5 link	c.10317C>T	p.Ile3439Ile	synonymous_variant	Exon 65 of 78	ENST00000420323.7	NP_056327.4
DNAH1	XM_017006129.2 link	c.10386C>T	p.Ile3462Ile	synonymous_variant	Exon 67 of 80		XP_016861618.1
DNAH1	XM_017006130.2 link	c.10317C>T	p.Ile3439Ile	synonymous_variant	Exon 66 of 79		XP_016861619.1
DNAH1	XM_017006131.2 link	c.10260C>T	p.Ile3420Ile	synonymous_variant	Exon 66 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
DNAH1	ENST00000420323.7 link	c.10317C>T	p.Ile3439Ile	synonymous_variant	Exon 65 of 78	1	NM_015512.5	ENSP00000401514.2
DNAH1	ENST00000486752.5 link	n.10774C>T		non_coding_transcript_exon_variant	Exon 64 of 77	2
DNAH1	ENST00000488988.5 link	n.2103C>T		non_coding_transcript_exon_variant	Exon 12 of 25	2
DNAH1	ENST00000490713.5 link	n.1017C>T		non_coding_transcript_exon_variant	Exon 8 of 20	5		ENSP00000419071.1

Frequencies

GnomAD3 genomes

AF:

0.0381

AC:

5665

AN:

148688

Hom.:

140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0206

Gnomad AMI

AF:

0.0837

Gnomad AMR

AF:

0.0487

Gnomad ASJ

AF:

0.0298

Gnomad EAS

AF:

0.0208

Gnomad SAS

AF:

0.0216

Gnomad FIN

AF:

0.0310

Gnomad MID

AF:

0.0387

Gnomad NFE

AF:

0.0494

Gnomad OTH

AF:

0.0432

GnomAD2 exomes

AF:

0.0373

AC:

9259

AN:

248252

AF XY:

0.0375

show subpopulations

Gnomad AFR exome

AF:

0.0218

Gnomad AMR exome

AF:

0.0340

Gnomad ASJ exome

AF:

0.0289

Gnomad EAS exome

AF:

0.0178

Gnomad FIN exome

AF:

0.0322

Gnomad NFE exome

AF:

0.0497

Gnomad OTH exome

AF:

0.0472

GnomAD4 exome

AF:

0.0453

AC:

66152

AN:

1459816

Hom.:

1646

Cov.:

AF XY:

0.0449

AC XY:

32611

AN XY:

726106

show subpopulations

African (AFR)

AF:

0.0230

AC:

768

AN:

33438

American (AMR)

AF:

0.0369

AC:

1648

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.0300

AC:

784

AN:

26102

East Asian (EAS)

AF:

0.0167

AC:

660

AN:

39542

South Asian (SAS)

AF:

0.0198

AC:

1709

AN:

86234

European-Finnish (FIN)

AF:

0.0334

AC:

1775

AN:

53194

Middle Eastern (MID)

AF:

0.0365

AC:

210

AN:

5758

European-Non Finnish (NFE)

AF:

0.0502

AC:

55791

AN:

1110608

Other (OTH)

AF:

0.0466

AC:

2807

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

3408

6815

10223

13630

17038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2042

4084

6126

8168

10210

<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:

0.0381

AC:

5666

AN:

148804

Hom.:

141

Cov.:

AF XY:

0.0359

AC XY:

2595

AN XY:

72374

show subpopulations

African (AFR)

AF:

0.0205

AC:

827

AN:

40292

American (AMR)

AF:

0.0487

AC:

721

AN:

14818

Ashkenazi Jewish (ASJ)

AF:

0.0298

AC:

103

AN:

3452

East Asian (EAS)

AF:

0.0204

AC:

102

AN:

4994

South Asian (SAS)

AF:

0.0214

AC:

AN:

4632

European-Finnish (FIN)

AF:

0.0310

AC:

311

AN:

10046

Middle Eastern (MID)

AF:

0.0414

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0494

AC:

3323

AN:

67324

Other (OTH)

AF:

0.0451

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

267

534

800

1067

1334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<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:

0.0479

Hom.:

310

Bravo

AF:

0.0395

Asia WGS

AF:

0.0360

AC:

123

AN:

3478

EpiCase

AF:

0.0501

EpiControl

AF:

0.0544

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 09, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.4

(source)

DANN

Benign

0.61

PhyloP100

-2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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