rs61734980

Variant names:

• chr16-20985659-G-C
• rs61734980
• NM_001347886.2:c.6945C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-20985659-G-C
• chr16-20985659-G-A

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.6945C>G​(p.Leu2315Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 1,614,154 control chromosomes in the GnomAD database, including 2,001 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (131 hom., cov: 31)
  • Exomes 𝑓: 0.047 (1870 hom.)
• Consequence: DNAH3 NM_001347886.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0920
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 16-20985659-G-C is Benign according to our data. Variant chr16-20985659-G-C is described in ClinVar as Benign. ClinVar VariationId is 402720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.092 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0517 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.6945C>G	p.Leu2315Leu	synonymous	Exon 48 of 62	NP_001334815.1	A0A8V8TLI9
	DNAH3	NM_017539.2		c.7083C>G	p.Leu2361Leu	synonymous	Exon 48 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.6945C>G	p.Leu2315Leu	synonymous	Exon 48 of 62	ENSP00000513632.1	A0A8V8TLI9
	DNAH3	ENST00000261383.3	TSL:1	c.7083C>G	p.Leu2361Leu	synonymous	Exon 48 of 62	ENSP00000261383.3	Q8TD57-1
	DNAH3	ENST00000685858.1		c.7125C>G	p.Leu2375Leu	synonymous	Exon 48 of 62	ENSP00000508756.1	A0A8I5KSE2

Frequencies

GnomAD3 genomes AF: 0.0355 AC: 5398 AN: 152154 Hom.: 131 Cov.: 31

Gnomad AFR AF: 0.00922

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.0352

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0531

Gnomad OTH AF: 0.0425

GnomAD2 exomes AF: 0.0364 AC: 9161 AN: 251422 AF XY: 0.0375

Gnomad AFR exome AF: 0.00548

Gnomad AMR exome AF: 0.0280

Gnomad ASJ exome AF: 0.0580

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0380

Gnomad NFE exome AF: 0.0527

Gnomad OTH exome AF: 0.0365

GnomAD4 exome AF: 0.0474 AC: 69321 AN: 1461882 Hom.: 1870 Cov.: 32 AF XY: 0.0468 AC XY: 34061 AN XY: 727240

African (AFR) AF: 0.00687 AC: 230 AN: 33480

American (AMR) AF: 0.0291 AC: 1301 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0598 AC: 1563 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0159 AC: 1374 AN: 86258

European-Finnish (FIN) AF: 0.0370 AC: 1978 AN: 53418

Middle Eastern (MID) AF: 0.0244 AC: 141 AN: 5768

European-Non Finnish (NFE) AF: 0.0540 AC: 60087 AN: 1112002

Other (OTH) AF: 0.0438 AC: 2645 AN: 60396

GnomAD4 genome AF: 0.0354 AC: 5396 AN: 152272 Hom.: 131 Cov.: 31 AF XY: 0.0346 AC XY: 2579 AN XY: 74456

African (AFR) AF: 0.00919 AC: 382 AN: 41564

American (AMR) AF: 0.0409 AC: 625 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0600 AC: 208 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.0143 AC: 69 AN: 4820

European-Finnish (FIN) AF: 0.0352 AC: 374 AN: 10618

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0531 AC: 3612 AN: 68016

Other (OTH) AF: 0.0416 AC: 88 AN: 2114

Alfa AF: 0.0409 Hom.: 54

Bravo AF: 0.0348

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	3.9
DANN	Benign	0.77
PhyloP100		0.092
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: rs61734980; hg19: chr16-20996981;