chr12-123781140-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001372106.1(DNAH10):c.682T>C(p.Ser228Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 1,613,600 control chromosomes in the GnomAD database, including 325,110 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30974 hom., cov: 30)

Exomes 𝑓: 0.63 ( 294136 hom. )

Consequence

DNAH10
NM_001372106.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.47

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1367255E-6).

BP6

Variant 12-123781140-T-C is Benign according to our data. Variant chr12-123781140-T-C is described in ClinVar as [Benign]. Clinvar id is 402611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-123781140-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH10	NM_001372106.1 link	c.682T>C	p.Ser228Pro	missense_variant	Exon 6 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.682T>C	p.Ser228Pro	missense_variant	Exon 6 of 79		NM_001372106.1	ENSP00000501095.1		A0A669KB38

Frequencies

GnomAD3 genomes

AF:

0.634

AC:

96171

AN:

151764

Hom.:

30940

Cov.:

show subpopulations

Gnomad AFR

AF:

0.565

Gnomad AMI

AF:

0.593

Gnomad AMR

AF:

0.692

Gnomad ASJ

AF:

0.685

Gnomad EAS

AF:

0.945

Gnomad SAS

AF:

0.702

Gnomad FIN

AF:

0.670

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.626

Gnomad OTH

AF:

0.644

GnomAD3 exomes

AF:

0.667

AC:

167460

AN:

251206

Hom.:

56911

AF XY:

0.666

AC XY:

90484

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.556

Gnomad AMR exome

AF:

0.696

Gnomad ASJ exome

AF:

0.684

Gnomad EAS exome

AF:

0.949

Gnomad SAS exome

AF:

0.675

Gnomad FIN exome

AF:

0.659

Gnomad NFE exome

AF:

0.626

Gnomad OTH exome

AF:

0.652

GnomAD4 exome

AF:

0.631

AC:

922399

AN:

1461720

Hom.:

294136

Cov.:

AF XY:

0.633

AC XY:

460440

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.551

Gnomad4 AMR exome

AF:

0.698

Gnomad4 ASJ exome

AF:

0.686

Gnomad4 EAS exome

AF:

0.950

Gnomad4 SAS exome

AF:

0.671

Gnomad4 FIN exome

AF:

0.667

Gnomad4 NFE exome

AF:

0.613

Gnomad4 OTH exome

AF:

0.644

GnomAD4 genome

AF:

0.634

AC:

96251

AN:

151880

Hom.:

30974

Cov.:

AF XY:

0.640

AC XY:

47528

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.565

Gnomad4 AMR

AF:

0.693

Gnomad4 ASJ

AF:

0.685

Gnomad4 EAS

AF:

0.945

Gnomad4 SAS

AF:

0.703

Gnomad4 FIN

AF:

0.670

Gnomad4 NFE

AF:

0.626

Gnomad4 OTH

AF:

0.648

Alfa

AF:

0.637

Hom.:

70459

Bravo

AF:

0.631

TwinsUK

AF:

0.612

AC:

2268

ALSPAC

AF:

0.604

AC:

2326

ESP6500AA

AF:

0.560

AC:

2468

ESP6500EA

AF:

0.630

AC:

5418

ExAC

AF:

0.663

AC:

80462

Asia WGS

AF:

0.808

AC:

2808

AN:

3478

EpiCase

AF:

0.622

EpiControl

AF:

0.630

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 19, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30389748, 31178129) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.062

DANN

Benign

0.68

DEOGEN2

Benign

0.0018

.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.33

T;T

MetaRNN

Benign

0.0000011

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.32

.;N

PrimateAI

Benign

0.34

REVEL

Benign

0.071

Polyphen

0.0

.;B

MPC

0.18

ClinPred

0.026

GERP RS

-11

Varity_R

0.064

gMVP

0.23

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

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