rs138940904

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015512.5(DNAH1):c.10915G>A(p.Ala3639Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,611,868 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

DNAH1
NM_015512.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.81

Publications

5 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.062885165).

BP6

Variant 3-52395006-G-A is Benign according to our data. Variant chr3-52395006-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 478392.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00127 (193/152298) while in subpopulation AMR AF = 0.00411 (63/15310). AF 95% confidence interval is 0.0033. There are 1 homozygotes in GnomAd4. There are 91 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 3 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5 link	c.10915G>A	p.Ala3639Thr	missense_variant	Exon 68 of 78	ENST00000420323.7	NP_056327.4	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006129.2 link	c.10984G>A	p.Ala3662Thr	missense_variant	Exon 70 of 80		XP_016861618.1
DNAH1	XM_017006130.2 link	c.10915G>A	p.Ala3639Thr	missense_variant	Exon 69 of 79		XP_016861619.1	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006131.2 link	c.10858G>A	p.Ala3620Thr	missense_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.10915G>A	p.Ala3639Thr	missense_variant	Exon 68 of 78	1	NM_015512.5	ENSP00000401514.2		Q9P2D7-4

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

193

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00144

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00129

AC:

315

AN:

244482

AF XY:

0.00133

show subpopulations

Gnomad AFR exome

AF:

0.000538

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.000908

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000752

Gnomad NFE exome

AF:

0.00183

Gnomad OTH exome

AF:

0.00185

GnomAD4 exome

AF:

0.00124

AC:

1812

AN:

1459570

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

846

AN XY:

725842

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33446

American (AMR)

AF:

0.00164

AC:

AN:

44454

Ashkenazi Jewish (ASJ)

AF:

0.000997

AC:

AN:

26068

East Asian (EAS)

AF:

0.00

AC:

AN:

39664

South Asian (SAS)

AF:

0.000210

AC:

AN:

85692

European-Finnish (FIN)

AF:

0.000677

AC:

AN:

53192

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00143

AC:

1585

AN:

1110990

Other (OTH)

AF:

0.00104

AC:

AN:

60296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

107

214

322

429

536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00127

AC:

193

AN:

152298

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41560

American (AMR)

AF:

0.00411

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00144

AC:

AN:

68010

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00153

Hom.:

Bravo

AF:

0.00134

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000965

AC:

ESP6500EA

AF:

0.00179

AC:

ExAC

AF:

0.00138

AC:

167

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

Benign:1

Jan 11, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.019

MetaRNN

Benign

0.063

MetaSVM

Benign

-0.87

PhyloP100

9.8

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.32

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.0080

Vest4

0.75

MVP

0.51

MPC

0.56

ClinPred

0.030

GERP RS

4.5

gMVP

0.73

Mutation Taster

=88/12

polymorphism

(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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rs138940904

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