rs16970881

Positions:

• chr16-21101951-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001347886.2(DNAH3):​c.2228+2520C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 152,278 control chromosomes in the GnomAD database, including 174 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.037 (174 hom., cov: 32)
• Consequence: DNAH3 NM_001347886.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH3	NM_001347886.2	c.2228+2520C>T		intron_variant		ENST00000698260.1	NP_001334815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH3	ENST00000698260.1	c.2228+2520C>T		intron_variant			NM_001347886.2	ENSP00000513632.1
DNAH3	ENST00000261383.3	c.2366+2520C>T		intron_variant		1		ENSP00000261383.3
DNAH3	ENST00000685858.1	c.2408+2520C>T		intron_variant				ENSP00000508756.1

Frequencies

GnomAD3 genomes AF: 0.0367 AC: 5579 AN: 152160 Hom.: 173 Cov.: 32

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0522

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.0335

Gnomad FIN AF: 0.0123

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0390

Gnomad OTH AF: 0.0516

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0367 AC: 5581 AN: 152278 Hom.: 174 Cov.: 32 AF XY: 0.0371 AC XY: 2761 AN XY: 74462

Gnomad4 AFR AF: 0.0126

Gnomad4 AMR AF: 0.0523

Gnomad4 ASJ AF: 0.0697

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.0332

Gnomad4 FIN AF: 0.0123

Gnomad4 NFE AF: 0.0390

Gnomad4 OTH AF: 0.0510

Alfa AF: 0.0425 Hom.: 382

Bravo AF: 0.0406

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.57

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: rs16970881; hg19: chr16-21113272;