NM_001369.3:c.13359A>G

Variant names:

• chr5-13701416-T-C
• rs3734111
• NM_001369.3:c.13359A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001369.3(DNAH5):​c.13359A>G​(p.Thr4453Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,605,764 control chromosomes in the GnomAD database, including 226,310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (18362 hom., cov: 30)
  • Exomes 𝑓: 0.53 (207948 hom.)
• Consequence: DNAH5 NM_001369.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -5.33
• Publications: 17 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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-13701416-T-C is Benign according to our data. Variant chr5-13701416-T-C is described in ClinVar as Benign. ClinVar VariationId is 178740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.33 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 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.13359A>G	p.Thr4453Thr	synonymous	Exon 77 of 79	NP_001360.1	Q8TE73

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.13359A>G	p.Thr4453Thr	synonymous	Exon 77 of 79	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.13314A>G	p.Thr4438Thr	synonymous	Exon 77 of 79	ENSP00000505288.1	A0A7P0Z455
	DNAH5	ENST00000683611.1		n.692A>G		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73509 AN: 151508 Hom.: 18346 Cov.: 30

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.499

GnomAD2 exomes AF: 0.503 AC: 126419 AN: 251126 AF XY: 0.503

Gnomad AFR exome AF: 0.371

Gnomad AMR exome AF: 0.493

Gnomad ASJ exome AF: 0.529

Gnomad EAS exome AF: 0.420

Gnomad FIN exome AF: 0.529

Gnomad NFE exome AF: 0.547

Gnomad OTH exome AF: 0.518

GnomAD4 exome AF: 0.531 AC: 772654 AN: 1454136 Hom.: 207948 Cov.: 44 AF XY: 0.529 AC XY: 382630 AN XY: 723818

African (AFR) AF: 0.360 AC: 12020 AN: 33362

American (AMR) AF: 0.493 AC: 22031 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 13730 AN: 26100

East Asian (EAS) AF: 0.388 AC: 15405 AN: 39662

South Asian (SAS) AF: 0.443 AC: 38174 AN: 86076

European-Finnish (FIN) AF: 0.528 AC: 28228 AN: 53416

Middle Eastern (MID) AF: 0.497 AC: 2861 AN: 5758

European-Non Finnish (NFE) AF: 0.551 AC: 609185 AN: 1104922

Other (OTH) AF: 0.516 AC: 31020 AN: 60124

GnomAD4 genome AF: 0.485 AC: 73568 AN: 151628 Hom.: 18362 Cov.: 30 AF XY: 0.482 AC XY: 35701 AN XY: 74066

African (AFR) AF: 0.375 AC: 15479 AN: 41256

American (AMR) AF: 0.499 AC: 7617 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 1858 AN: 3468

East Asian (EAS) AF: 0.433 AC: 2234 AN: 5156

South Asian (SAS) AF: 0.446 AC: 2146 AN: 4810

European-Finnish (FIN) AF: 0.530 AC: 5540 AN: 10462

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36957 AN: 67914

Other (OTH) AF: 0.501 AC: 1055 AN: 2106

Alfa AF: 0.524 Hom.: 61742

Bravo AF: 0.479

Asia WGS AF: 0.455 AC: 1584 AN: 3478

EpiCase AF: 0.540

EpiControl AF: 0.552

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Primary ciliary dyskinesia (3)
-	-	3	Primary ciliary dyskinesia 3 (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0020
DANN	Benign	0.49
PhyloP100		-5.3
Mutation Taster		=81/19	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: rs3734111; hg19: chr5-13701525; COSMIC: COSV54212349;