NM_001369.3:c.58-764T>C

Variant names:

• chr5-13932008-A-G
• rs1530495
• NM_001369.3:c.58-764T>C

Variant summary

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

The NM_001369.3(DNAH5):​c.58-764T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,148 control chromosomes in the GnomAD database, including 14,396 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 0.41 (14393 hom., cov: 33)
  • Exomes 𝑓: 0.18 (3 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 0 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.58-764T>C		intron	N/A	NP_001360.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.58-764T>C		intron	N/A	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.13-764T>C		intron	N/A	ENSP00000505288.1
	DNAH5	ENST00000508040.1	TSL:2	n.416+33T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62238 AN: 151964 Hom.: 14370 Cov.: 33

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.407

GnomAD4 exome AF: 0.182 AC: 12 AN: 66 Hom.: 3 Cov.: 0 AF XY: 0.239 AC XY: 11 AN XY: 46

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.161 AC: 9 AN: 56

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.410 AC: 62310 AN: 152082 Hom.: 14393 Cov.: 33 AF XY: 0.408 AC XY: 30361 AN XY: 74342

African (AFR) AF: 0.607 AC: 25156 AN: 41468

American (AMR) AF: 0.397 AC: 6059 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1199 AN: 3466

East Asian (EAS) AF: 0.698 AC: 3615 AN: 5178

South Asian (SAS) AF: 0.375 AC: 1807 AN: 4818

European-Finnish (FIN) AF: 0.284 AC: 3000 AN: 10576

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20264 AN: 67988

Other (OTH) AF: 0.407 AC: 857 AN: 2108

Alfa AF: 0.360 Hom.: 1937

Bravo AF: 0.427

Asia WGS AF: 0.515 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.31
PhyloP100		-1.1
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: rs1530495; hg19: chr5-13932117;