dbSNP rs58411567: DNAH10:p.Glu3243Glu (chr12-123903027-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001372106.1(DNAH10):c.9729G>A(p.Glu3243Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,604,564 control chromosomes in the GnomAD database, including 49,530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7823 hom., cov: 33)

Exomes 𝑓: 0.24 ( 41707 hom. )

Consequence

DNAH10
NM_001372106.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.983

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 12-123903027-G-A is Benign according to our data. Variant chr12-123903027-G-A is described in ClinVar as [Benign]. Clinvar id is 402621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-123903027-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.983 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH10	NM_001372106.1 link	c.9729G>A	p.Glu3243Glu	synonymous_variant	Exon 57 of 79	ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH10	ENST00000673944.1 link	c.9729G>A	p.Glu3243Glu	synonymous_variant	Exon 57 of 79		NM_001372106.1	ENSP00000501095.1	A0A669KB38
DNAH10	ENST00000409039.8 link	c.9558G>A	p.Glu3186Glu	synonymous_variant	Exon 56 of 78	5		ENSP00000386770.4	A0A1C7CYW8
DNAH10	ENST00000638045.1 link	c.9375G>A	p.Glu3125Glu	synonymous_variant	Exon 56 of 78	5		ENSP00000489675.1	Q8IVF4-1

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45869

AN:

151810

Hom.:

7816

Cov.:

show subpopulations

Gnomad AFR

AF:

0.478

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.262

Gnomad ASJ

AF:

0.214

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.305

GnomAD3 exomes

AF:

0.246

AC:

57839

AN:

234970

Hom.:

7433

AF XY:

0.242

AC XY:

30809

AN XY:

127288

show subpopulations

Gnomad AFR exome

AF:

0.482

Gnomad AMR exome

AF:

0.253

Gnomad ASJ exome

AF:

0.209

Gnomad EAS exome

AF:

0.252

Gnomad SAS exome

AF:

0.237

Gnomad FIN exome

AF:

0.225

Gnomad NFE exome

AF:

0.222

Gnomad OTH exome

AF:

0.247

GnomAD4 exome

AF:

0.237

AC:

343905

AN:

1452636

Hom.:

41707

Cov.:

AF XY:

0.236

AC XY:

170277

AN XY:

721702

show subpopulations

Gnomad4 AFR exome

AF:

0.489

Gnomad4 AMR exome

AF:

0.255

Gnomad4 ASJ exome

AF:

0.208

Gnomad4 EAS exome

AF:

0.266

Gnomad4 SAS exome

AF:

0.241

Gnomad4 FIN exome

AF:

0.235

Gnomad4 NFE exome

AF:

0.227

Gnomad4 OTH exome

AF:

0.254

GnomAD4 genome

AF:

0.302

AC:

45916

AN:

151928

Hom.:

7823

Cov.:

AF XY:

0.300

AC XY:

22293

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.478

Gnomad4 AMR

AF:

0.262

Gnomad4 ASJ

AF:

0.214

Gnomad4 EAS

AF:

0.269

Gnomad4 SAS

AF:

0.249

Gnomad4 FIN

AF:

0.232

Gnomad4 NFE

AF:

0.227

Gnomad4 OTH

AF:

0.303

Alfa

AF:

0.257

Hom.:

2399

Bravo

AF:

0.314

Asia WGS

AF:

0.303

AC:

1051

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

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: 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: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.8

DANN

Benign

0.39

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