rs61735917

Positions:

• chr12-123898714-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001372106.1(DNAH10):​c.9540C>T​(p.Asp3180Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.005 in 1,604,774 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0087 (10 hom., cov: 33)
  • Exomes 𝑓: 0.0046 (24 hom.)
• Consequence: DNAH10 NM_001372106.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.412

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 12-123898714-C-T is Benign according to our data. Variant chr12-123898714-C-T is described in ClinVar as [Benign]. Clinvar id is 402620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-123898714-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.412 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0087 (1325/152360) while in subpopulation AFR AF= 0.0193 (802/41584). AF 95% confidence interval is 0.0182. There are 10 homozygotes in gnomad4. There are 626 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH10	NM_001372106.1	c.9540C>T	p.Asp3180Asp	synonymous_variant	56/79	ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH10	ENST00000673944.1	c.9540C>T	p.Asp3180Asp	synonymous_variant	56/79		NM_001372106.1	ENSP00000501095.1
DNAH10	ENST00000409039.8	c.9369C>T	p.Asp3123Asp	synonymous_variant	55/78	5		ENSP00000386770.4
DNAH10	ENST00000638045.1	c.9186C>T	p.Asp3062Asp	synonymous_variant	55/78	5		ENSP00000489675.1

Frequencies

GnomAD3 genomes AF: 0.00870 AC: 1324 AN: 152242 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00876

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00555

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00445

Gnomad OTH AF: 0.00907

GnomAD3 exomes AF: 0.00516 AC: 1189 AN: 230510 Hom.: 5 AF XY: 0.00471 AC XY: 589 AN XY: 125052

Gnomad AFR exome AF: 0.0200

Gnomad AMR exome AF: 0.00737

Gnomad ASJ exome AF: 0.00145

Gnomad EAS exome AF: 0.0000599

Gnomad SAS exome AF: 0.000142

Gnomad FIN exome AF: 0.00494

Gnomad NFE exome AF: 0.00513

Gnomad OTH exome AF: 0.00423

GnomAD4 exome AF: 0.00461 AC: 6699 AN: 1452414 Hom.: 24 Cov.: 31 AF XY: 0.00450 AC XY: 3248 AN XY: 721432

Gnomad4 AFR exome AF: 0.0183

Gnomad4 AMR exome AF: 0.00816

Gnomad4 ASJ exome AF: 0.00170

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.000143

Gnomad4 FIN exome AF: 0.00477

Gnomad4 NFE exome AF: 0.00461

Gnomad4 OTH exome AF: 0.00488

GnomAD4 genome AF: 0.00870 AC: 1325 AN: 152360 Hom.: 10 Cov.: 33 AF XY: 0.00840 AC XY: 626 AN XY: 74510

Gnomad4 AFR AF: 0.0193

Gnomad4 AMR AF: 0.00875

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00555

Gnomad4 NFE AF: 0.00445

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.00596 Hom.: 2

Bravo AF: 0.00985

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 28, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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, silent variant not in splice consensus -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	1.5
DANN	Benign	0.79

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: rs61735917; hg19: chr12-124383261; COSMIC: COSV101293096;