rs75558206

chr12-123903122-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001372106.1(DNAH10):c.9815+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0418 in 1,600,364 control chromosomes in the GnomAD database, including 4,711 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (2119 hom., cov: 33)
  • Exomes 𝑓: 0.035 (2592 hom.)
• Consequence: DNAH10 NM_001372106.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0920

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-123903122-C-T is Benign according to our data. Variant chr12-123903122-C-T is described in ClinVar as [Benign]. Clinvar id is 402623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-123903122-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH10	NM_001372106.1	c.9815+9C>T		intron_variant		ENST00000673944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH10	ENST00000673944.1	c.9815+9C>T		intron_variant			NM_001372106.1	P1
DNAH10	ENST00000409039.8	c.9644+9C>T		intron_variant		5
DNAH10	ENST00000638045.1	c.9461+9C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16476 AN: 152080 Hom.: 2113 Cov.: 33

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0678

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.00434

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0277

Gnomad OTH AF: 0.101

GnomAD3 exomes AF: 0.0423 AC: 9608 AN: 227000 Hom.: 763 AF XY: 0.0379 AC XY: 4667 AN XY: 123070

Gnomad AFR exome AF: 0.314

Gnomad AMR exome AF: 0.0409

Gnomad ASJ exome AF: 0.0685

Gnomad EAS exome AF: 0.000833

Gnomad SAS exome AF: 0.0187

Gnomad FIN exome AF: 0.00418

Gnomad NFE exome AF: 0.0256

Gnomad OTH exome AF: 0.0436

GnomAD4 exome AF: 0.0348 AC: 50390 AN: 1448166 Hom.: 2592 Cov.: 32 AF XY: 0.0336 AC XY: 24155 AN XY: 718816

Gnomad4 AFR exome AF: 0.331

Gnomad4 AMR exome AF: 0.0426

Gnomad4 ASJ exome AF: 0.0710

Gnomad4 EAS exome AF: 0.000613

Gnomad4 SAS exome AF: 0.0198

Gnomad4 FIN exome AF: 0.00422

Gnomad4 NFE exome AF: 0.0275

Gnomad4 OTH exome AF: 0.0506

GnomAD4 genome AF: 0.108 AC: 16506 AN: 152198 Hom.: 2119 Cov.: 33 AF XY: 0.105 AC XY: 7776 AN XY: 74410

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.0677

Gnomad4 ASJ AF: 0.0769

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.00434

Gnomad4 NFE AF: 0.0277

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0755 Hom.: 484

Bravo AF: 0.124

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.9
Dann	Benign	0.22

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

Other links and lift over

dbSNP: rs75558206; hg19: chr12-124387669;