Genetic Variant NM_001372106.1:c.13392C>T (chr12-123933426-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001372106.1(DNAH10):c.13392C>T(p.Asn4464Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,612,662 control chromosomes in the GnomAD database, including 354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 19 hom., cov: 33)

Exomes 𝑓: 0.019 ( 335 hom. )

Consequence

DNAH10
NM_001372106.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.02

Publications

4 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 12-123933426-C-T is Benign according to our data. Variant chr12-123933426-C-T is described in ClinVar as Benign. ClinVar VariationId is 402626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.02 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0136 (2078/152322) while in subpopulation NFE AF = 0.0206 (1399/68024). AF 95% confidence interval is 0.0197. There are 19 homozygotes in GnomAd4. There are 948 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 19 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAH10	NM_001372106.1	MANE Select	c.13392C>T	p.Asn4464Asn	synonymous	Exon 77 of 79	NP_001359035.1
DNAH10	NM_207437.3		c.13038C>T	p.Asn4346Asn	synonymous	Exon 76 of 78	NP_997320.2
DNAH10OS	NR_187476.1		n.920+639G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAH10	ENST00000673944.1	MANE Select	c.13392C>T	p.Asn4464Asn	synonymous	Exon 77 of 79	ENSP00000501095.1
DNAH10	ENST00000409039.8	TSL:5	c.13221C>T	p.Asn4407Asn	synonymous	Exon 76 of 78	ENSP00000386770.4
DNAH10	ENST00000638045.1	TSL:5	c.13038C>T	p.Asn4346Asn	synonymous	Exon 76 of 78	ENSP00000489675.1

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

2081

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00391

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0130

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0102

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0206

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.0138

AC:

3407

AN:

247454

AF XY:

0.0145

show subpopulations

Gnomad AFR exome

AF:

0.00331

Gnomad AMR exome

AF:

0.00876

Gnomad ASJ exome

AF:

0.0185

Gnomad EAS exome

AF:

0.00106

Gnomad FIN exome

AF:

0.0113

Gnomad NFE exome

AF:

0.0200

Gnomad OTH exome

AF:

0.0152

GnomAD4 exome

AF:

0.0192

AC:

27981

AN:

1460340

Hom.:

335

Cov.:

AF XY:

0.0191

AC XY:

13842

AN XY:

726482

show subpopulations

African (AFR)

AF:

0.00347

AC:

116

AN:

33442

American (AMR)

AF:

0.00871

AC:

389

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

565

AN:

26128

East Asian (EAS)

AF:

0.000807

AC:

AN:

39658

South Asian (SAS)

AF:

0.00986

AC:

850

AN:

86168

European-Finnish (FIN)

AF:

0.0109

AC:

575

AN:

52700

Middle Eastern (MID)

AF:

0.0282

AC:

156

AN:

5538

European-Non Finnish (NFE)

AF:

0.0218

AC:

24197

AN:

1111696

Other (OTH)

AF:

0.0183

AC:

1101

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

1651

3303

4954

6606

8257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

924

1848

2772

3696

4620

<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:

0.0136

AC:

2078

AN:

152322

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

948

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00390

AC:

162

AN:

41578

American (AMR)

AF:

0.0129

AC:

198

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0231

AC:

AN:

3470

East Asian (EAS)

AF:

0.00174

AC:

AN:

5186

South Asian (SAS)

AF:

0.0102

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0104

AC:

111

AN:

10628

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0206

AC:

1399

AN:

68024

Other (OTH)

AF:

0.0132

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

105

210

316

421

526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0167

Hom.:

Bravo

AF:

0.0137

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Silent, not in splice consensus

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

2.6

(source)

DANN

Benign

0.88

PhyloP100

-2.0

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over