16-20935342-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001347886.2(DNAH3):c.11859+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,613,896 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (60 hom.)
• Consequence: DNAH3 NM_001347886.2 splice_donor_region, intron
• Scores: Splicing: ADA: 0.00002575
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.52

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-20935342-C-T is Benign according to our data. Variant chr16-20935342-C-T is described in ClinVar as [Benign]. Clinvar id is 713290.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00139 (212/152160) while in subpopulation EAS AF= 0.0246 (127/5172). AF 95% confidence interval is 0.0211. There are 3 homozygotes in gnomad4. There are 120 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 212 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH3	NM_001347886.2	c.11859+6G>A		splice_donor_region_variant, intron_variant		ENST00000698260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH3	ENST00000698260.1	c.11859+6G>A		splice_donor_region_variant, intron_variant			NM_001347886.2	P1
DNAH3	ENST00000261383.3	c.11997+6G>A		splice_donor_region_variant, intron_variant		1
DNAH3	ENST00000685858.1	c.12039+6G>A		splice_donor_region_variant, intron_variant

Frequencies

GnomAD3 genomes AF: 0.00139 AC: 212 AN: 152042 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0245

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00466 AC: 1170 AN: 251246 Hom.: 10 AF XY: 0.00380 AC XY: 516 AN XY: 135796

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0196

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0257

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00179 AC: 2620 AN: 1461736 Hom.: 60 Cov.: 31 AF XY: 0.00167 AC XY: 1213 AN XY: 727160

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.0175

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0433

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000899

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome AF: 0.00139 AC: 212 AN: 152160 Hom.: 3 Cov.: 32 AF XY: 0.00161 AC XY: 120 AN XY: 74384

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.00504

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0246

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000239 Hom.: 1

Bravo AF: 0.00219

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.0000545

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

Sep 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.37
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000026
dbscSNV1_RF	Benign	0.0
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: rs2301618; hg19: chr16-20946664;