16-20933391-G-A

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.11976C>T(p.Leu3992=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00343 in 1,614,156 control chromosomes in the GnomAD database, including 179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (80 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (99 hom.)
• Consequence: DNAH3 NM_001347886.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.861

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=-0.57).
• BP6: Variant 16-20933391-G-A is Benign according to our data. Variant chr16-20933391-G-A is described in ClinVar as [Benign]. Clinvar id is 776990.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.861 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH3	NM_001347886.2	c.11976C>T	p.Leu3992=	synonymous_variant	62/62	ENST00000698260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH3	ENST00000698260.1	c.11976C>T	p.Leu3992=	synonymous_variant	62/62		NM_001347886.2	P1
DNAH3	ENST00000261383.3	c.12114C>T	p.Leu4038=	synonymous_variant	62/62	1
DNAH3	ENST00000685858.1	c.12156C>T	p.Leu4052=	synonymous_variant	62/62

Frequencies

GnomAD3 genomes AF: 0.0177 AC: 2691 AN: 152182 Hom.: 80 Cov.: 33

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00463 AC: 1162 AN: 250994 Hom.: 27 AF XY: 0.00332 AC XY: 451 AN XY: 135692

Gnomad AFR exome AF: 0.0615

Gnomad AMR exome AF: 0.00367

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00195 AC: 2848 AN: 1461856 Hom.: 99 Cov.: 31 AF XY: 0.00162 AC XY: 1180 AN XY: 727226

Gnomad4 AFR exome AF: 0.0666

Gnomad4 AMR exome AF: 0.00427

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000243

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000103

Gnomad4 OTH exome AF: 0.00457

GnomAD4 genome AF: 0.0177 AC: 2696 AN: 152300 Hom.: 80 Cov.: 33 AF XY: 0.0171 AC XY: 1275 AN XY: 74478

Gnomad4 AFR AF: 0.0609

Gnomad4 AMR AF: 0.00784

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.00664 Hom.: 12

Bravo AF: 0.0209

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.0000593

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	-0.57
Cadd	Benign	3.9
Dann	Benign	0.78

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: rs13336534; hg19: chr16-20944713;