NM_001369.3:c.7888-4392T>G

Variant names:

• chr5-13798450-A-C
• rs795544
• NM_001369.3:c.7888-4392T>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.7888-4392T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,066 control chromosomes in the GnomAD database, including 48,907 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 0.80 (48907 hom., cov: 31)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.7888-4392T>G		intron_variant	Intron 47 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.7888-4392T>G		intron_variant	Intron 47 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.7843-4392T>G		intron_variant	Intron 47 of 78			ENSP00000505288.1

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121651 AN: 151948 Hom.: 48873 Cov.: 31

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.801 AC: 121745 AN: 152066 Hom.: 48907 Cov.: 31 AF XY: 0.795 AC XY: 59113 AN XY: 74338

African (AFR) AF: 0.821 AC: 34089 AN: 41510

American (AMR) AF: 0.825 AC: 12612 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3038 AN: 3470

East Asian (EAS) AF: 0.879 AC: 4542 AN: 5166

South Asian (SAS) AF: 0.647 AC: 3117 AN: 4818

European-Finnish (FIN) AF: 0.697 AC: 7332 AN: 10524

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.797 AC: 54188 AN: 67980

Other (OTH) AF: 0.823 AC: 1736 AN: 2110

Alfa AF: 0.806 Hom.: 89846

Bravo AF: 0.818

Asia WGS AF: 0.742 AC: 2580 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.89
DANN	Benign	0.87
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: rs795544; hg19: chr5-13798559;