Variant chr12-123933342-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001372106.1(DNAH10):c.13308C>T(p.Ser4436=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,572,818 control chromosomes in the GnomAD database, including 72,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7065 hom., cov: 33)

Exomes 𝑓: 0.30 ( 65737 hom. )

Consequence

DNAH10
NM_001372106.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.63

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 12-123933342-C-T is Benign according to our data. Variant chr12-123933342-C-T is described in ClinVar as [Benign]. Clinvar id is 402625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-123933342-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.63 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH10	NM_001372106.1 linkuse as main transcript	c.13308C>T	p.Ser4436=	synonymous_variant	77/79	ENST00000673944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH10	ENST00000673944.1 linkuse as main transcript	c.13308C>T	p.Ser4436=	synonymous_variant	77/79		NM_001372106.1	P1
DNAH10OS	ENST00000514254.3 linkuse as main transcript	n.920+723G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

46013

AN:

151996

Hom.:

7062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.371

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.317

Gnomad OTH

AF:

0.325

GnomAD3 exomes

AF:

0.276

AC:

60043

AN:

217258

Hom.:

8616

AF XY:

0.277

AC XY:

32849

AN XY:

118510

show subpopulations

Gnomad AFR exome

AF:

0.314

Gnomad AMR exome

AF:

0.237

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.114

Gnomad SAS exome

AF:

0.207

Gnomad FIN exome

AF:

0.269

Gnomad NFE exome

AF:

0.321

Gnomad OTH exome

AF:

0.301

GnomAD4 exome

AF:

0.300

AC:

426778

AN:

1420704

Hom.:

65737

Cov.:

AF XY:

0.299

AC XY:

210179

AN XY:

703514

show subpopulations

Gnomad4 AFR exome

AF:

0.319

Gnomad4 AMR exome

AF:

0.245

Gnomad4 ASJ exome

AF:

0.348

Gnomad4 EAS exome

AF:

0.137

Gnomad4 SAS exome

AF:

0.210

Gnomad4 FIN exome

AF:

0.285

Gnomad4 NFE exome

AF:

0.314

Gnomad4 OTH exome

AF:

0.303

GnomAD4 genome

AF:

0.303

AC:

46042

AN:

152114

Hom.:

7065

Cov.:

AF XY:

0.297

AC XY:

22095

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.321

Gnomad4 AMR

AF:

0.284

Gnomad4 ASJ

AF:

0.348

Gnomad4 EAS

AF:

0.127

Gnomad4 SAS

AF:

0.215

Gnomad4 FIN

AF:

0.270

Gnomad4 NFE

AF:

0.317

Gnomad4 OTH

AF:

0.322

Alfa

AF:

0.311

Hom.:

3672

Bravo

AF:

0.307

Asia WGS

AF:

0.208

AC:

725

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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: Frequency -

DNAH10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.013

DANN

Benign

0.77

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over