Variant chr12-123925083-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BA1

The NM_001372106.1(DNAH10):c.11800G>T(p.Val3934Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,613,890 control chromosomes in the GnomAD database, including 1,517 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 (no stars).

Frequency

Genomes: 𝑓 0.057 ( 748 hom., cov: 33)

Exomes 𝑓: 0.0089 ( 769 hom. )

Consequence

DNAH10
NM_001372106.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.28

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:

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 -12 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=0.0055770874).

BP6

Variant 12-123925083-G-T is Benign according to our data. Variant chr12-123925083-G-T is described in ClinVar as [Benign]. Clinvar id is 3347651.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-123925083-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 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.11800G>T	p.Val3934Phe	missense_variant	68/79	ENST00000673944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH10	ENST00000673944.1 linkuse as main transcript	c.11800G>T	p.Val3934Phe	missense_variant	68/79		NM_001372106.1	P1

Frequencies

GnomAD3 genomes

AF:

0.0567

AC:

8616

AN:

152088

Hom.:

747

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0306

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.00407

Gnomad OTH

AF:

0.0522

GnomAD3 exomes

AF:

0.0178

AC:

4427

AN:

249188

Hom.:

313

AF XY:

0.0143

AC XY:

1933

AN XY:

135196

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.0170

Gnomad ASJ exome

AF:

0.0219

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00206

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00386

Gnomad OTH exome

AF:

0.0157

GnomAD4 exome

AF:

0.00888

AC:

12984

AN:

1461684

Hom.:

769

Cov.:

AF XY:

0.00823

AC XY:

5982

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.0187

Gnomad4 ASJ exome

AF:

0.0215

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00196

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.00302

Gnomad4 OTH exome

AF:

0.0193

GnomAD4 genome

AF:

0.0567

AC:

8632

AN:

152206

Hom.:

748

Cov.:

AF XY:

0.0548

AC XY:

4080

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.0305

Gnomad4 ASJ

AF:

0.0219

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00407

Gnomad4 OTH

AF:

0.0521

Alfa

AF:

0.00756

Hom.:

Bravo

AF:

0.0662

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.182

AC:

709

ESP6500EA

AF:

0.00470

AC:

ExAC

AF:

0.0199

AC:

2407

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DNAH10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 15, 2024

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.7

DANN

Benign

0.59

DEOGEN2

Benign

0.00096

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.089

T;T

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.1

.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

REVEL

Benign

0.049

Polyphen

0.0

.;B

MPC

0.19

ClinPred

0.0016

GERP RS

1.5

Varity_R

0.048

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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