Genetic Variant DNAH10:p.Ser297Ser (chr12-123783156-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

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

The NM_001372106.1(DNAH10):c.891T>C(p.Ser297Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,613,770 control chromosomes in the GnomAD database, including 318,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 36227 hom., cov: 32)

Exomes 𝑓: 0.62 ( 282012 hom. )

Consequence

DNAH10
NM_001372106.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.47

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:

LOC105370044 (HGNC:):

LOC105370044 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=-0.93).

BP6

Variant 12-123783156-T-C is Benign according to our data. Variant chr12-123783156-T-C is described in ClinVar as [Benign]. Clinvar id is 402613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-123783156-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.47 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH10	NM_001372106.1 link	c.891T>C	p.Ser297Ser	synonymous_variant	Exon 7 of 79	ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH10	ENST00000673944.1 link	c.891T>C	p.Ser297Ser	synonymous_variant	Exon 7 of 79		NM_001372106.1	ENSP00000501095.1		A0A669KB38

Frequencies

GnomAD3 genomes

AF:

0.681

AC:

103481

AN:

151948

Hom.:

36168

Cov.:

show subpopulations

Gnomad AFR

AF:

0.786

Gnomad AMI

AF:

0.473

Gnomad AMR

AF:

0.721

Gnomad ASJ

AF:

0.692

Gnomad EAS

AF:

0.996

Gnomad SAS

AF:

0.720

Gnomad FIN

AF:

0.610

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.595

Gnomad OTH

AF:

0.680

GnomAD3 exomes

AF:

0.673

AC:

169105

AN:

251448

Hom.:

58643

AF XY:

0.666

AC XY:

90570

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.786

Gnomad AMR exome

AF:

0.729

Gnomad ASJ exome

AF:

0.694

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

0.696

Gnomad FIN exome

AF:

0.604

Gnomad NFE exome

AF:

0.593

Gnomad OTH exome

AF:

0.646

GnomAD4 exome

AF:

0.615

AC:

899276

AN:

1461704

Hom.:

282012

Cov.:

AF XY:

0.617

AC XY:

448832

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.792

Gnomad4 AMR exome

AF:

0.729

Gnomad4 ASJ exome

AF:

0.696

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.692

Gnomad4 FIN exome

AF:

0.609

Gnomad4 NFE exome

AF:

0.583

Gnomad4 OTH exome

AF:

0.642

GnomAD4 genome

AF:

0.681

AC:

103595

AN:

152066

Hom.:

36227

Cov.:

AF XY:

0.686

AC XY:

50967

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.786

Gnomad4 AMR

AF:

0.722

Gnomad4 ASJ

AF:

0.692

Gnomad4 EAS

AF:

0.996

Gnomad4 SAS

AF:

0.721

Gnomad4 FIN

AF:

0.610

Gnomad4 NFE

AF:

0.595

Gnomad4 OTH

AF:

0.684

Alfa

AF:

0.620

Hom.:

54989

Bravo

AF:

0.693

Asia WGS

AF:

0.867

AC:

3012

AN:

3478

EpiCase

AF:

0.595

EpiControl

AF:

0.607

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: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0050

DANN

Benign

0.46

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