rs4701995

chr5-13868428-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001369.3(DNAH5):c.3835-436C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,052 control chromosomes in the GnomAD database, including 12,023 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 0.39 (12023 hom., cov: 32)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH5	NM_001369.3	c.3835-436C>T		intron_variant		ENST00000265104.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH5	ENST00000265104.5	c.3835-436C>T		intron_variant		1	NM_001369.3	P4
	ENST00000503244.2	n.253+7873G>A		intron_variant, non_coding_transcript_variant		4
DNAH5	ENST00000681290.1	c.3790-436C>T		intron_variant				A1
	ENST00000637153.1	n.213+7913G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59364 AN: 151934 Hom.: 12005 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.391 AC: 59425 AN: 152052 Hom.: 12023 Cov.: 32 AF XY: 0.390 AC XY: 28962 AN XY: 74310

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.401

Alfa AF: 0.435 Hom.: 7514

Bravo AF: 0.370

Asia WGS AF: 0.382 AC: 1330 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.3
Dann	Benign	0.71

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: rs4701995; hg19: chr5-13868537;