chr12-123771606-C-T

Position:

chr12-123771606-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2

The NM_001372106.1(DNAH10):c.304C>T(p.Arg102Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000468 in 1,613,236 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00057 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00046 ( 2 hom. )

Consequence

DNAH10
NM_001372106.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.605

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 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=0.0057855844).

BP6

Variant 12-123771606-C-T is Benign according to our data. Variant chr12-123771606-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3049615.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH10	NM_001372106.1 linkuse as main transcript	c.304C>T	p.Arg102Cys	missense_variant	3/79	ENST00000673944.1	NP_001359035.1
LOC105370044	XR_945481.4 linkuse as main transcript	n.496-6358G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH10	ENST00000673944.1 linkuse as main transcript	c.304C>T	p.Arg102Cys	missense_variant	3/79		NM_001372106.1	ENSP00000501095	P1
DNAH10	ENST00000409039.8 linkuse as main transcript	c.304C>T	p.Arg102Cys	missense_variant	3/78	5		ENSP00000386770
DNAH10	ENST00000638045.1 linkuse as main transcript	c.121C>T	p.Arg41Cys	missense_variant	3/78	5		ENSP00000489675		Q8IVF4-1
DNAH10	ENST00000614082.1 linkuse as main transcript	c.-426C>T		5_prime_UTR_variant	3/20	5		ENSP00000479072

Frequencies

GnomAD3 genomes

AF:

0.000572

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000677

AC:

168

AN:

248106

Hom.:

AF XY:

0.000832

AC XY:

112

AN XY:

134562

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000872

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00145

Gnomad FIN exome

AF:

0.00288

Gnomad NFE exome

AF:

0.000480

Gnomad OTH exome

AF:

0.000830

GnomAD4 exome

AF:

0.000457

AC:

668

AN:

1460972

Hom.:

Cov.:

AF XY:

0.000553

AC XY:

402

AN XY:

726682

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00172

Gnomad4 FIN exome

AF:

0.00337

Gnomad4 NFE exome

AF:

0.000270

Gnomad4 OTH exome

AF:

0.000547

GnomAD4 genome

AF:

0.000571

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000445

Hom.:

Bravo

AF:

0.000223

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000365

AC:

ExAC

AF:

0.000737

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000297

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DNAH10-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as likely 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

0.11

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.51

DEOGEN2

Benign

0.0021

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.42

T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

REVEL

Benign

0.041

Polyphen

0.13

.;B

MVP

0.061

MPC

0.20

ClinPred

0.021

GERP RS

-0.59

Varity_R

0.069

gMVP

0.29

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