rs34934281

Positions:

chr12-123845764-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_001372106.1(DNAH10):c.5525C>T(p.Thr1842Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,613,898 control chromosomes in the GnomAD database, including 10,189 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 682 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9507 hom. )

Consequence

DNAH10
NM_001372106.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.60

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 -19 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DNAH10. . Gene score misZ 1.5457 (greater than the threshold 3.09). Trascript score misZ 3.4903 (greater than threshold 3.09). GenCC has associacion of gene with spermatogenic failure 56.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024943054).

BP6

Variant 12-123845764-C-T is Benign according to our data. Variant chr12-123845764-C-T is described in ClinVar as [Benign]. Clinvar id is 402616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-123845764-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 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.5525C>T	p.Thr1842Met	missense_variant	31/79	ENST00000673944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH10	ENST00000673944.1 linkuse as main transcript	c.5525C>T	p.Thr1842Met	missense_variant	31/79		NM_001372106.1	P1
DNAH10	ENST00000409039.8 linkuse as main transcript	c.5354C>T	p.Thr1785Met	missense_variant	30/78	5
DNAH10	ENST00000638045.1 linkuse as main transcript	c.5171C>T	p.Thr1724Met	missense_variant	30/78	5			Q8IVF4-1
DNAH10	ENST00000497783.3 linkuse as main transcript	c.713C>T	p.Thr238Met	missense_variant, NMD_transcript_variant	4/21	2

Frequencies

GnomAD3 genomes

AF:

0.0823

AC:

12510

AN:

152090

Hom.:

681

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0233

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.0928

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0592

Gnomad FIN

AF:

0.0720

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.103

GnomAD3 exomes

AF:

0.0866

AC:

21594

AN:

249236

Hom.:

1154

AF XY:

0.0891

AC XY:

12054

AN XY:

135212

show subpopulations

Gnomad AFR exome

AF:

0.0224

Gnomad AMR exome

AF:

0.0634

Gnomad ASJ exome

AF:

0.126

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0644

Gnomad FIN exome

AF:

0.0777

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.109

AC:

159130

AN:

1461690

Hom.:

9507

Cov.:

AF XY:

0.108

AC XY:

78864

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.0240

Gnomad4 AMR exome

AF:

0.0674

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0673

Gnomad4 FIN exome

AF:

0.0856

Gnomad4 NFE exome

AF:

0.121

Gnomad4 OTH exome

AF:

0.100

GnomAD4 genome

AF:

0.0822

AC:

12513

AN:

152208

Hom.:

682

Cov.:

AF XY:

0.0789

AC XY:

5869

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0233

Gnomad4 AMR

AF:

0.0926

Gnomad4 ASJ

AF:

0.126

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0599

Gnomad4 FIN

AF:

0.0720

Gnomad4 NFE

AF:

0.121

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.110

Hom.:

1646

Bravo

AF:

0.0824

TwinsUK

AF:

0.119

AC:

442

ALSPAC

AF:

0.121

AC:

467

ESP6500AA

AF:

0.0235

AC:

ESP6500EA

AF:

0.117

AC:

982

ExAC

AF:

0.0872

AC:

10550

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

EpiCase

AF:

0.126

EpiControl

AF:

0.129

ClinVar

Significance: Benign

Submissions summary: Benign:2

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: MAF -

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

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0032

.;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

.;M

MutationTaster

Benign

0.090

PrimateAI

Benign

0.43

REVEL

Benign

0.071

Polyphen

0.47

.;P

MPC

0.16

ClinPred

0.019

GERP RS

4.9

Varity_R

0.027

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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