Variant rs56219209 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001372106.1(DNAH10):c.13392C>T(p.Asn4464Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,612,662 control chromosomes in the GnomAD database, including 354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 19 hom., cov: 33)

Exomes 𝑓: 0.019 ( 335 hom. )

Consequence

DNAH10
NM_001372106.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.02

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:

DNAH10OS (HGNC:37121): (dynein axonemal heavy chain 10 opposite strand)

DNAH10OS 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 12-123933426-C-T is Benign according to our data. Variant chr12-123933426-C-T is described in ClinVar as [Benign]. Clinvar id is 402626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-123933426-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.02 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0136 (2078/152322) while in subpopulation NFE AF= 0.0206 (1399/68024). AF 95% confidence interval is 0.0197. There are 19 homozygotes in gnomad4. There are 948 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH10	NM_001372106.1 link	c.13392C>T	p.Asn4464Asn	synonymous_variant	77/79	ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH10	ENST00000673944.1 link	c.13392C>T	p.Asn4464Asn	synonymous_variant	77/79		NM_001372106.1	ENSP00000501095.1		A0A669KB38

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

2081

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00391

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0130

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0102

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0206

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0138

AC:

3407

AN:

247454

Hom.:

AF XY:

0.0145

AC XY:

1946

AN XY:

134584

show subpopulations

Gnomad AFR exome

AF:

0.00331

Gnomad AMR exome

AF:

0.00876

Gnomad ASJ exome

AF:

0.0185

Gnomad EAS exome

AF:

0.00106

Gnomad SAS exome

AF:

0.00902

Gnomad FIN exome

AF:

0.0113

Gnomad NFE exome

AF:

0.0200

Gnomad OTH exome

AF:

0.0152

GnomAD4 exome

AF:

0.0192

AC:

27981

AN:

1460340

Hom.:

335

Cov.:

AF XY:

0.0191

AC XY:

13842

AN XY:

726482

show subpopulations

Gnomad4 AFR exome

AF:

0.00347

Gnomad4 AMR exome

AF:

0.00871

Gnomad4 ASJ exome

AF:

0.0216

Gnomad4 EAS exome

AF:

0.000807

Gnomad4 SAS exome

AF:

0.00986

Gnomad4 FIN exome

AF:

0.0109

Gnomad4 NFE exome

AF:

0.0218

Gnomad4 OTH exome

AF:

0.0183

GnomAD4 genome

AF:

0.0136

AC:

2078

AN:

152322

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

948

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00390

Gnomad4 AMR

AF:

0.0129

Gnomad4 ASJ

AF:

0.0231

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0102

Gnomad4 FIN

AF:

0.0104

Gnomad4 NFE

AF:

0.0206

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.0167

Hom.:

Bravo

AF:

0.0137

Asia WGS

AF:

0.0150

AC:

AN:

3478

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: Silent, not in splice consensus -

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

BayesDel_noAF

Benign

-0.35

CADD

Benign

2.6

DANN

Benign

0.88

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