dbSNP rs764960821: DNAH10:p.Leu3865Ile (chr12-123923849-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001372106.1(DNAH10):c.11593C>A(p.Leu3865Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000665 in 1,609,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

DNAH10
NM_001372106.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.45

Publications

1 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 links:

CCDC92 (HGNC:29563): (coiled-coil domain containing 92) Enables identical protein binding activity. Located in centriole; centrosome; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CCDC92 links:

LOC124903043 (HGNC:):

LOC124903043 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2142038).

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.11593C>A	p.Leu3865Ile	missense	Exon 66 of 79	NP_001359035.1	A0A669KB38
	DNAH10	NM_207437.3		c.11239C>A	p.Leu3747Ile	missense	Exon 65 of 78	NP_997320.2	B0I1S1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH10	ENST00000673944.1	MANE Select	c.11593C>A	p.Leu3865Ile	missense	Exon 66 of 79	ENSP00000501095.1	A0A669KB38
DNAH10	ENST00000409039.8	TSL:5	c.11422C>A	p.Leu3808Ile	missense	Exon 65 of 78	ENSP00000386770.4	A0A1C7CYW8
DNAH10	ENST00000638045.1	TSL:5	c.11239C>A	p.Leu3747Ile	missense	Exon 65 of 78	ENSP00000489675.1	Q8IVF4-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152018

Hom.:

Cov.:

show subpopulations

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000123

AC:

AN:

244702

AF XY:

0.0000226

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000269

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000720

AC:

105

AN:

1457642

Hom.:

Cov.:

AF XY:

0.0000648

AC XY:

AN XY:

724928

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33232

American (AMR)

AF:

0.00

AC:

AN:

43854

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26040

East Asian (EAS)

AF:

0.00

AC:

AN:

39628

South Asian (SAS)

AF:

0.00

AC:

AN:

84996

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000918

AC:

102

AN:

1110594

Other (OTH)

AF:

0.0000498

AC:

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

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

AF:

0.0000132

AC:

AN:

152018

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41392

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.36

CADD

Benign

0.13

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0045

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.10

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.029

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.31

MutationAssessor

Pathogenic

3.2

PhyloP100

-1.4

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.35

Sift

Benign

0.12

Polyphen

0.93

MutPred

0.53

Gain of methylation at K3752 (P = 0.0466)

MVP

0.22

MPC

0.26

ClinPred

0.52

GERP RS

-6.0

Varity_R

0.096

gMVP

0.24

Mutation Taster

=71/29

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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