16-20952443-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001347886.2(DNAH3):c.11040C>G(p.Thr3680=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00452 in 1,604,990 control chromosomes in the GnomAD database, including 301 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (179 hom., cov: 31)
  • Exomes 𝑓: 0.0023 (122 hom.)
• Consequence: DNAH3 NM_001347886.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.411

Genes affected

DNAH3 (HGNC:2949): (dynein axonemal heavy chain 3) This gene belongs to the dynein family, whose members encode large proteins that are constituents of the microtubule-associated motor protein complex. This complex is composed of dynein heavy, intermediate and light chains, which can be axonemal or cytoplasmic. This protein is an axonemal dynein heavy chain. It is involved in producing force for ciliary beating by using energy from ATP hydrolysis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 16-20952443-G-C is Benign according to our data. Variant chr16-20952443-G-C is described in ClinVar as [Benign]. Clinvar id is 718594.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.411 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.086 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH3	NM_001347886.2	c.11040C>G	p.Thr3680=	synonymous_variant	56/62	ENST00000698260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH3	ENST00000698260.1	c.11040C>G	p.Thr3680=	synonymous_variant	56/62		NM_001347886.2	P1
DNAH3	ENST00000261383.3	c.11178C>G	p.Thr3726=	synonymous_variant	56/62	1
DNAH3	ENST00000685858.1	c.11220C>G	p.Thr3740=	synonymous_variant	56/62

Frequencies

GnomAD3 genomes AF: 0.0253 AC: 3844 AN: 152050 Hom.: 179 Cov.: 31

Gnomad AFR AF: 0.0884

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00885

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000831

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0144

GnomAD3 exomes AF: 0.00691 AC: 1737 AN: 251324 Hom.: 68 AF XY: 0.00457 AC XY: 621 AN XY: 135818

Gnomad AFR exome AF: 0.0913

Gnomad AMR exome AF: 0.00515

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.00619

GnomAD4 exome AF: 0.00234 AC: 3406 AN: 1452822 Hom.: 122 Cov.: 28 AF XY: 0.00202 AC XY: 1459 AN XY: 723446

Gnomad4 AFR exome AF: 0.0796

Gnomad4 AMR exome AF: 0.00573

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000256

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000111

Gnomad4 OTH exome AF: 0.00573

GnomAD4 genome AF: 0.0253 AC: 3854 AN: 152168 Hom.: 179 Cov.: 31 AF XY: 0.0243 AC XY: 1808 AN XY: 74404

Gnomad4 AFR AF: 0.0884

Gnomad4 AMR AF: 0.00884

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000831

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00173 Hom.: 2

Bravo AF: 0.0286

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	3.3
Dann	Benign	0.70

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: rs7199676; hg19: chr16-20963765;