Genetic Variant NM_001372106.1:c.12215G>A (chr12-123928496-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001372106.1(DNAH10):c.12215G>A(p.Arg4072Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,611,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

DNAH10
NM_001372106.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62

Publications

0 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:

DNAH10OS (HGNC:37121): (dynein axonemal heavy chain 10 opposite strand)

DNAH10OS 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019210577).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH10	NM_001372106.1	MANE Select	c.12215G>A	p.Arg4072Lys	missense	Exon 70 of 79	NP_001359035.1	A0A669KB38
DNAH10	NM_207437.3		c.11861G>A	p.Arg3954Lys	missense	Exon 69 of 78	NP_997320.2	B0I1S1
DNAH10OS	NR_187476.1		n.2968C>T		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH10	ENST00000673944.1	MANE Select	c.12215G>A	p.Arg4072Lys	missense	Exon 70 of 79	ENSP00000501095.1	A0A669KB38
DNAH10	ENST00000409039.8	TSL:5	c.12044G>A	p.Arg4015Lys	missense	Exon 69 of 78	ENSP00000386770.4	A0A1C7CYW8
DNAH10	ENST00000638045.1	TSL:5	c.11861G>A	p.Arg3954Lys	missense	Exon 69 of 78	ENSP00000489675.1	Q8IVF4-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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

GnomAD2 exomes

AF:

0.000144

AC:

AN:

243394

AF XY:

0.000128

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000999

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000470

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1459174

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

725650

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33428

American (AMR)

AF:

0.000856

AC:

AN:

44392

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26014

East Asian (EAS)

AF:

0.00

AC:

AN:

39642

South Asian (SAS)

AF:

0.00

AC:

AN:

85586

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110918

Other (OTH)

AF:

0.00

AC:

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

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:

0.0000197

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.000196

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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:

0.0000522

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.000108

AC:

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

0.066

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.00078

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.78

M_CAP

Benign

0.0041

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.12

PhyloP100

2.6

PrimateAI

Benign

0.36

REVEL

Benign

0.064

Polyphen

0.0010

MutPred

0.37

Gain of ubiquitination at R3954 (P = 0.0408)

MVP

0.14

MPC

0.15

ClinPred

0.047

GERP RS

1.4

Varity_R

0.11

gMVP

0.24

Mutation Taster

=87/13

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

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