rs33935373

Variant names:

Variant summary

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

The NM_001372106.1(DNAH10):c.6311C>T(p.Thr2104Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0359 in 1,603,722 control chromosomes in the GnomAD database, including 1,220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 61 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1159 hom. )

Consequence

DNAH10
NM_001372106.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.89

Publications

10 publications found

Variant links:

Genes affected

DNAH10 (HGNC:2941): (dynein axonemal heavy chain 10) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. The axonemal dyneins, found in cilia and flagella, are components of the outer and inner dynein arms attached to the peripheral microtubule doublets. DNAH10 is an inner arm dynein heavy chain (Maiti et al., 2000 [PubMed 11175280]).[supplied by OMIM, Mar 2008]

DNAH10 Gene-Disease associations (from GenCC):

spermatogenic failure 56
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
primary ciliary dyskinesia
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

DNAH10 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001372106.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008422822).

BP6

Variant 12-123853225-C-T is Benign according to our data. Variant chr12-123853225-C-T is described in ClinVar as Benign. ClinVar VariationId is 402617.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 = 0.0244 (3704/151884) while in subpopulation NFE AF = 0.0385 (2615/67984). AF 95% confidence interval is 0.0372. There are 61 homozygotes in GnomAd4. There are 1828 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 61 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372106.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH10	NM_001372106.1	MANE Select	c.6311C>T	p.Thr2104Met	missense	Exon 36 of 79	NP_001359035.1	A0A669KB38
	DNAH10	NM_207437.3		c.5957C>T	p.Thr1986Met	missense	Exon 35 of 78	NP_997320.2	B0I1S1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH10	ENST00000673944.1	MANE Select	c.6311C>T	p.Thr2104Met	missense	Exon 36 of 79	ENSP00000501095.1	A0A669KB38
DNAH10	ENST00000409039.8	TSL:5	c.6140C>T	p.Thr2047Met	missense	Exon 35 of 78	ENSP00000386770.4	A0A1C7CYW8
DNAH10	ENST00000638045.1	TSL:5	c.5957C>T	p.Thr1986Met	missense	Exon 35 of 78	ENSP00000489675.1	Q8IVF4-1

Frequencies

GnomAD3 genomes

AF:

0.0244

AC:

3706

AN:

151766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00686

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.00932

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0341

Gnomad FIN

AF:

0.0396

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0385

Gnomad OTH

AF:

0.0211

GnomAD2 exomes

AF:

0.0281

AC:

6706

AN:

238310

AF XY:

0.0298

show subpopulations

Gnomad AFR exome

AF:

0.00515

Gnomad AMR exome

AF:

0.00989

Gnomad ASJ exome

AF:

0.00751

Gnomad EAS exome

AF:

0.000287

Gnomad FIN exome

AF:

0.0374

Gnomad NFE exome

AF:

0.0395

Gnomad OTH exome

AF:

0.0280

GnomAD4 exome

AF:

0.0372

AC:

53941

AN:

1451838

Hom.:

1159

Cov.:

AF XY:

0.0370

AC XY:

26705

AN XY:

721618

show subpopulations

African (AFR)

AF:

0.00551

AC:

183

AN:

33208

American (AMR)

AF:

0.0104

AC:

450

AN:

43276

Ashkenazi Jewish (ASJ)

AF:

0.00790

AC:

204

AN:

25814

East Asian (EAS)

AF:

0.000380

AC:

AN:

39506

South Asian (SAS)

AF:

0.0357

AC:

3021

AN:

84556

European-Finnish (FIN)

AF:

0.0371

AC:

1962

AN:

52940

Middle Eastern (MID)

AF:

0.0162

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.0417

AC:

46197

AN:

1106828

Other (OTH)

AF:

0.0303

AC:

1816

AN:

59974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

2492

4984

7476

9968

12460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1684

3368

5052

6736

8420

<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:

0.0244

AC:

3704

AN:

151884

Hom.:

Cov.:

AF XY:

0.0246

AC XY:

1828

AN XY:

74178

show subpopulations

African (AFR)

AF:

0.00684

AC:

283

AN:

41384

American (AMR)

AF:

0.00931

AC:

142

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5164

South Asian (SAS)

AF:

0.0341

AC:

164

AN:

4806

European-Finnish (FIN)

AF:

0.0396

AC:

416

AN:

10502

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0385

AC:

2615

AN:

67984

Other (OTH)

AF:

0.0209

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

190

380

571

761

951

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0341

Hom.:

316

Bravo

AF:

0.0208

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

MetaRNN

Benign

0.0084

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.4

PhyloP100

7.9

PrimateAI

Uncertain

0.79

REVEL

Uncertain

0.30

Varity_R

0.69

gMVP

0.61

Mutation Taster

=38/62

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over