rs3734109

Variant names:

• chr5-13735783-T-C
• rs3734109
• NM_001369.3:c.11570+35A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-13735783-T-C
• chr5-13735783-T-A
• chr5-13735783-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001369.3(DNAH5):​c.11570+35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,466,164 control chromosomes in the GnomAD database, including 248,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (24929 hom., cov: 33)
  • Exomes 𝑓: 0.58 (223884 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -6.08
• Publications: 13 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 5-13735783-T-C is Benign according to our data. Variant chr5-13735783-T-C is described in ClinVar as Benign. ClinVar VariationId is 257980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.582 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.11570+35A>G		intron	N/A	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.11570+35A>G		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.11525+35A>G		intron	N/A	ENSP00000505288.1	A0A7P0Z455

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86783 AN: 151984 Hom.: 24916 Cov.: 33

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.571

GnomAD2 exomes AF: 0.574 AC: 143834 AN: 250574 AF XY: 0.574

Gnomad AFR exome AF: 0.526

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.572

Gnomad EAS exome AF: 0.590

Gnomad FIN exome AF: 0.654

Gnomad NFE exome AF: 0.584

Gnomad OTH exome AF: 0.576

GnomAD4 exome AF: 0.582 AC: 764659 AN: 1314062 Hom.: 223884 Cov.: 19 AF XY: 0.581 AC XY: 385102 AN XY: 662578

African (AFR) AF: 0.530 AC: 16127 AN: 30416

American (AMR) AF: 0.539 AC: 23989 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 14679 AN: 25230

East Asian (EAS) AF: 0.582 AC: 22662 AN: 38910

South Asian (SAS) AF: 0.542 AC: 45075 AN: 83224

European-Finnish (FIN) AF: 0.650 AC: 34643 AN: 53318

Middle Eastern (MID) AF: 0.557 AC: 3048 AN: 5472

European-Non Finnish (NFE) AF: 0.586 AC: 572482 AN: 977480

Other (OTH) AF: 0.576 AC: 31954 AN: 55474

GnomAD4 genome AF: 0.571 AC: 86846 AN: 152102 Hom.: 24929 Cov.: 33 AF XY: 0.575 AC XY: 42754 AN XY: 74348

African (AFR) AF: 0.526 AC: 21814 AN: 41476

American (AMR) AF: 0.564 AC: 8623 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2005 AN: 3472

East Asian (EAS) AF: 0.573 AC: 2965 AN: 5178

South Asian (SAS) AF: 0.544 AC: 2623 AN: 4822

European-Finnish (FIN) AF: 0.664 AC: 7026 AN: 10576

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.587 AC: 39910 AN: 67988

Other (OTH) AF: 0.571 AC: 1205 AN: 2112

Alfa AF: 0.578 Hom.: 99185

Bravo AF: 0.561

Asia WGS AF: 0.543 AC: 1888 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0010
DANN	Benign	0.40
PhyloP100		-6.1
Mutation Taster		=99/1	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: rs3734109; hg19: chr5-13735892; COSMIC: COSV54227665;