rs3777093

Variant names:

• chr5-13729605-A-G
• rs3777093
• NM_001369.3:c.11762-45T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-13729605-A-G
• chr5-13729605-A-T

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.11762-45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 1,526,076 control chromosomes in the GnomAD database, including 265,948 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27631 hom., cov: 33)
  • Exomes 𝑓: 0.59 (238317 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.06
• Publications: 8 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
• 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=-0.96).
• BP6: Variant 5-13729605-A-G is Benign according to our data. Variant chr5-13729605-A-G is described in ClinVar as Benign. ClinVar VariationId is 257985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.11762-45T>C		intron	N/A	NP_001360.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.11762-45T>C		intron	N/A	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.11717-45T>C		intron	N/A	ENSP00000505288.1

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91453 AN: 151946 Hom.: 27613 Cov.: 33

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.597

GnomAD2 exomes AF: 0.596 AC: 122829 AN: 206150 AF XY: 0.593

Gnomad AFR exome AF: 0.620

Gnomad AMR exome AF: 0.566

Gnomad ASJ exome AF: 0.580

Gnomad EAS exome AF: 0.634

Gnomad FIN exome AF: 0.679

Gnomad NFE exome AF: 0.592

Gnomad OTH exome AF: 0.590

GnomAD4 exome AF: 0.588 AC: 807975 AN: 1374012 Hom.: 238317 Cov.: 21 AF XY: 0.587 AC XY: 401445 AN XY: 684132

African (AFR) AF: 0.617 AC: 18733 AN: 30378

American (AMR) AF: 0.568 AC: 23564 AN: 41464

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 14703 AN: 25118

East Asian (EAS) AF: 0.669 AC: 24407 AN: 36468

South Asian (SAS) AF: 0.547 AC: 43501 AN: 79470

European-Finnish (FIN) AF: 0.670 AC: 34310 AN: 51234

Middle Eastern (MID) AF: 0.552 AC: 2639 AN: 4778

European-Non Finnish (NFE) AF: 0.585 AC: 612715 AN: 1048218

Other (OTH) AF: 0.587 AC: 33403 AN: 56884

GnomAD4 genome AF: 0.602 AC: 91528 AN: 152064 Hom.: 27631 Cov.: 33 AF XY: 0.606 AC XY: 45071 AN XY: 74326

African (AFR) AF: 0.616 AC: 25536 AN: 41466

American (AMR) AF: 0.587 AC: 8963 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2009 AN: 3470

East Asian (EAS) AF: 0.623 AC: 3223 AN: 5176

South Asian (SAS) AF: 0.550 AC: 2653 AN: 4822

European-Finnish (FIN) AF: 0.684 AC: 7224 AN: 10560

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39983 AN: 67974

Other (OTH) AF: 0.596 AC: 1258 AN: 2112

Alfa AF: 0.596 Hom.: 16367

Bravo AF: 0.594

Asia WGS AF: 0.581 AC: 2016 AN: 3472

ClinVar

ClinVar submissions as Germline

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	-0.96
CADD	Benign	0.019
DANN	Benign	0.49
PhyloP100		-3.1
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: rs3777093; hg19: chr5-13729714;