NM_001347886.2:c.11976C>T

Variant names:

• chr16-20933391-G-A
• rs13336534
• NM_001347886.2:c.11976C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001347886.2(DNAH3):​c.11976C>T​(p.Leu3992Leu) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.861
• Publications: 3 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 -21 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 VariationId is 776990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.

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.11976C>T	p.Leu3992Leu	synonymous	Exon 62 of 62	NP_001334815.1	A0A8V8TLI9
	DNAH3	NM_017539.2		c.12114C>T	p.Leu4038Leu	synonymous	Exon 62 of 62	NP_060009.1	Q8TD57-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH3	ENST00000698260.1	MANE Select	c.11976C>T	p.Leu3992Leu	synonymous	Exon 62 of 62	ENSP00000513632.1	A0A8V8TLI9
	DNAH3	ENST00000261383.3	TSL:1	c.12114C>T	p.Leu4038Leu	synonymous	Exon 62 of 62	ENSP00000261383.3	Q8TD57-1
	DNAH3	ENST00000685858.1		c.12156C>T	p.Leu4052Leu	synonymous	Exon 62 of 62	ENSP00000508756.1	A0A8I5KSE2

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

GnomAD2 exomes AF: 0.00463 AC: 1162 AN: 250994 AF XY: 0.00332

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 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

African (AFR) AF: 0.0666 AC: 2229 AN: 33480

American (AMR) AF: 0.00427 AC: 191 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000243 AC: 21 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00261 AC: 15 AN: 5742

European-Non Finnish (NFE) AF: 0.000103 AC: 114 AN: 1112008

Other (OTH) AF: 0.00457 AC: 276 AN: 60392

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

African (AFR) AF: 0.0609 AC: 2530 AN: 41550

American (AMR) AF: 0.00784 AC: 120 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68032

Other (OTH) AF: 0.0133 AC: 28 AN: 2112

Alfa AF: 0.00696 Hom.: 15

Bravo AF: 0.0209

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	3.9
DANN	Benign	0.78
PhyloP100		0.86
Mutation Taster		=97/3	polymorphism

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: rs13336534; hg19: chr16-20944713;