Genetic Variant DNAH10:p.Glu3243Asp (chr12-123903027-G-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001372106.1(DNAH10):c.9729G>C(p.Glu3243Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E3243E) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000030 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAH10
NM_001372106.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.983

Publications

11 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: LIMITED Submitted by: Ambry Genetics

DNAH10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.39898333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH10	NM_001372106.1 link	c.9729G>C	p.Glu3243Asp	missense_variant	Exon 57 of 79	ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH10	ENST00000673944.1 link	c.9729G>C	p.Glu3243Asp	missense_variant	Exon 57 of 79		NM_001372106.1	ENSP00000501095.1	A0A669KB38
DNAH10	ENST00000409039.8 link	c.9558G>C	p.Glu3186Asp	missense_variant	Exon 56 of 78	5		ENSP00000386770.4	A0A1C7CYW8
DNAH10	ENST00000638045.1 link	c.9375G>C	p.Glu3125Asp	missense_variant	Exon 56 of 78	5		ENSP00000489675.1	Q8IVF4-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151876

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000303

AC:

AN:

1453354

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

722126

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000301

AC:

AN:

33198

American (AMR)

AF:

0.0000690

AC:

AN:

43466

Ashkenazi Jewish (ASJ)

AF:

0.0000770

AC:

AN:

25982

East Asian (EAS)

AF:

0.000127

AC:

AN:

39316

South Asian (SAS)

AF:

0.00

AC:

AN:

84716

European-Finnish (FIN)

AF:

0.0000379

AC:

AN:

52774

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1108052

Other (OTH)

AF:

0.0000499

AC:

AN:

60088

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.235

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151994

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74324

African (AFR)

AF:

0.00

AC:

AN:

41366

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67982

Other (OTH)

AF:

0.00

AC:

AN:

2110

Alfa

AF:

0.00

Hom.:

2399

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

.;T

Eigen

Benign

-0.033

Eigen_PC

Benign

-0.015

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-0.41

MutationAssessor

Uncertain

2.5

.;M

PhyloP100

0.98

PrimateAI

Uncertain

0.50

REVEL

Benign

0.27

Polyphen

0.52

.;P

MutPred

0.33

.;Gain of glycosylation at T3126 (P = 0.1212);

MVP

0.53

MPC

0.16

ClinPred

0.92

GERP RS

3.1

Varity_R

0.22

gMVP

0.56

Mutation Taster

=87/13

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over