5-13937367-T-C

Variant names:

• chr5-13937367-T-C
• rs17278234
• NM_001369.3:c.58-6123A>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.58-6123A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 150,658 control chromosomes in the GnomAD database, including 4,960 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 0.25 (4960 hom., cov: 26)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.58-6123A>G		intron_variant	Intron 1 of 78	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.58-6123A>G		intron_variant	Intron 1 of 78	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.13-6123A>G		intron_variant	Intron 1 of 78			ENSP00000505288.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37039 AN: 150540 Hom.: 4956 Cov.: 26

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0225

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.246 AC: 37054 AN: 150658 Hom.: 4960 Cov.: 26 AF XY: 0.239 AC XY: 17573 AN XY: 73470

African (AFR) AF: 0.200 AC: 8152 AN: 40858

American (AMR) AF: 0.261 AC: 3927 AN: 15024

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 928 AN: 3464

East Asian (EAS) AF: 0.0226 AC: 116 AN: 5134

South Asian (SAS) AF: 0.165 AC: 778 AN: 4712

European-Finnish (FIN) AF: 0.224 AC: 2341 AN: 10428

Middle Eastern (MID) AF: 0.259 AC: 75 AN: 290

European-Non Finnish (NFE) AF: 0.294 AC: 19919 AN: 67754

Other (OTH) AF: 0.232 AC: 486 AN: 2092

Alfa AF: 0.278 Hom.: 11405

Bravo AF: 0.249

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.68
PhyloP100		0.079
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: rs17278234; hg19: chr5-13937476;