5-13868428-G-A

Variant names:

• chr5-13868428-G-A
• rs4701995
• NM_001369.3:c.3835-436C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAH5-AS1 (HGNC:40187):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.3835-436C>T		intron	N/A	NP_001360.1	Q8TE73
	DNAH5-AS1	NR_199035.1		n.117+7873G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.3835-436C>T		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.3790-436C>T		intron	N/A	ENSP00000505288.1	A0A7P0Z455
	DNAH5-AS1	ENST00000503244.2	TSL:4	n.253+7873G>A		intron	N/A

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

African (AFR) AF: 0.301 AC: 12475 AN: 41480

American (AMR) AF: 0.340 AC: 5197 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1234 AN: 3468

East Asian (EAS) AF: 0.261 AC: 1351 AN: 5174

South Asian (SAS) AF: 0.464 AC: 2233 AN: 4816

European-Finnish (FIN) AF: 0.487 AC: 5147 AN: 10566

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30544 AN: 67976

Other (OTH) AF: 0.401 AC: 844 AN: 2106

Alfa AF: 0.433 Hom.: 8260

Bravo AF: 0.370

Asia WGS AF: 0.382 AC: 1330 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.71
PhyloP100		0.20
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: rs4701995; hg19: chr5-13868537;