chr16-21101951-G-A

Variant names:

• chr16-21101951-G-A
• rs16970881
• NM_001347886.2:c.2228+2520C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

DNAH3 Gene-Disease associations (from GenCC):

• male infertility

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347886.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH3	NM_001347886.2	MANE Select	c.2228+2520C>T		intron	N/A	NP_001334815.1
	DNAH3	NM_017539.2		c.2366+2520C>T		intron	N/A	NP_060009.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH3	ENST00000698260.1	MANE Select	c.2228+2520C>T		intron	N/A	ENSP00000513632.1
	DNAH3	ENST00000261383.3	TSL:1	c.2366+2520C>T		intron	N/A	ENSP00000261383.3
	DNAH3	ENST00000685858.1		c.2408+2520C>T		intron	N/A	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

African (AFR) AF: 0.0126 AC: 524 AN: 41556

American (AMR) AF: 0.0523 AC: 800 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0697 AC: 242 AN: 3470

East Asian (EAS) AF: 0.175 AC: 908 AN: 5180

South Asian (SAS) AF: 0.0332 AC: 160 AN: 4826

European-Finnish (FIN) AF: 0.0123 AC: 130 AN: 10606

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0390 AC: 2652 AN: 68024

Other (OTH) AF: 0.0510 AC: 108 AN: 2116

Alfa AF: 0.0409 Hom.: 584

Bravo AF: 0.0406

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.57
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16970881; hg19: chr16-21113272;