5-13937367-T-C

Position:

• chr5-13937367-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.58-6123A>G		intron_variant		ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.58-6123A>G		intron_variant		1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.13-6123A>G		intron_variant				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

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.0226

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.232

Alfa AF: 0.279 Hom.: 8127

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs17278234; hg19: chr5-13937476;