12-123909293-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001372106.1(DNAH10):c.9848C>T(p.Thr3283Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,613,458 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 6 hom. )

Consequence

DNAH10
NM_001372106.1 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.13

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012706608).

BP6

Variant 12-123909293-C-T is Benign according to our data. Variant chr12-123909293-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 402627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH10	NM_001372106.1 link	c.9848C>T	p.Thr3283Met	missense_variant	Exon 58 of 79	ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH10	ENST00000673944.1 link	c.9848C>T	p.Thr3283Met	missense_variant	Exon 58 of 79		NM_001372106.1	ENSP00000501095.1	A0A669KB38
DNAH10	ENST00000409039.8 link	c.9677C>T	p.Thr3226Met	missense_variant	Exon 57 of 78	5		ENSP00000386770.4	A0A1C7CYW8
DNAH10	ENST00000638045.1 link	c.9494C>T	p.Thr3165Met	missense_variant	Exon 57 of 78	5		ENSP00000489675.1	Q8IVF4-1
DNAH10	ENST00000540041.2 link	c.233C>T	p.Thr78Met	missense_variant	Exon 2 of 5	5		ENSP00000445308.2	H0YGZ2

Frequencies

GnomAD3 genomes

AF:

0.00183

AC:

278

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00235

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00158

AC:

390

AN:

247452

Hom.:

AF XY:

0.00162

AC XY:

218

AN XY:

134586

show subpopulations

Gnomad AFR exome

AF:

0.000262

Gnomad AMR exome

AF:

0.00180

Gnomad ASJ exome

AF:

0.00110

Gnomad EAS exome

AF:

0.0000558

Gnomad SAS exome

AF:

0.00109

Gnomad FIN exome

AF:

0.000697

Gnomad NFE exome

AF:

0.00226

Gnomad OTH exome

AF:

0.00183

GnomAD4 exome

AF:

0.00239

AC:

3495

AN:

1461116

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

1648

AN XY:

726720

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00222

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00103

Gnomad4 FIN exome

AF:

0.000620

Gnomad4 NFE exome

AF:

0.00276

Gnomad4 OTH exome

AF:

0.00245

GnomAD4 genome

AF:

0.00182

AC:

278

AN:

152342

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

125

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00516

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00235

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00215

Hom.:

Bravo

AF:

0.00275

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000257

AC:

ESP6500EA

AF:

0.00229

AC:

ExAC

AF:

0.00133

AC:

161

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00284

EpiControl

AF:

0.00238

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DNAH10: BS2 -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely 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: Other variants in this gene questionably associated with sperm immotility. No information about this variant. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

.;T;.

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.94

D;D;.

M_CAP

Benign

0.025

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.74

.;N;.

PrimateAI

Uncertain

0.54

REVEL

Benign

0.20

Sift4G

Uncertain

0.0050

.;.;D

Polyphen

0.77

.;P;.

MVP

0.63

MPC

0.17

ClinPred

0.021

GERP RS

5.6

Varity_R

0.070

gMVP

0.37

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