rs39829

Variant names:

• chr5-13719888-A-C
• rs39829
• NM_001369.3:c.12280-787T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001369.3(DNAH5):​c.12280-787T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,950 control chromosomes in the GnomAD database, including 13,848 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 0.42 (13848 hom., cov: 32)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 1 publications found

Genes affected

DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]

DNAH5 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369.3. 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
	DNAH5	NM_001369.3	MANE Select	c.12280-787T>G		intron	N/A	NP_001360.1	Q8TE73

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.12280-787T>G		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.12235-787T>G		intron	N/A	ENSP00000505288.1	A0A7P0Z455

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64410 AN: 151830 Hom.: 13822 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.424 AC: 64482 AN: 151950 Hom.: 13848 Cov.: 32 AF XY: 0.420 AC XY: 31157 AN XY: 74244

African (AFR) AF: 0.468 AC: 19395 AN: 41428

American (AMR) AF: 0.427 AC: 6527 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1466 AN: 3466

East Asian (EAS) AF: 0.378 AC: 1952 AN: 5162

South Asian (SAS) AF: 0.461 AC: 2223 AN: 4820

European-Finnish (FIN) AF: 0.317 AC: 3337 AN: 10538

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28157 AN: 67942

Other (OTH) AF: 0.420 AC: 888 AN: 2116

Alfa AF: 0.418 Hom.: 10455

Bravo AF: 0.435

Asia WGS AF: 0.435 AC: 1515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.43
PhyloP100		-1.5
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs39829;

hg19: chr5-13719997;