rs10513153

Variant names:

• chr5-13769891-C-T
• rs10513153
• NM_001369.3:c.9606-276G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001369.3(DNAH5):​c.9606-276G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,028 control chromosomes in the GnomAD database, including 8,255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (8255 hom., cov: 34)
• Consequence: DNAH5 NM_001369.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.977
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 5-13769891-C-T is Benign according to our data. Variant chr5-13769891-C-T is described in ClinVar as Benign. ClinVar VariationId is 1235747.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.362 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.9606-276G>A		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.9606-276G>A		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.9561-276G>A		intron	N/A	ENSP00000505288.1	A0A7P0Z455
	DNAH5	ENST00000504001.3	TSL:5	n.318-276G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49372 AN: 151910 Hom.: 8256 Cov.: 34

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.325 AC: 49378 AN: 152028 Hom.: 8255 Cov.: 34 AF XY: 0.324 AC XY: 24045 AN XY: 74286

African (AFR) AF: 0.251 AC: 10417 AN: 41478

American (AMR) AF: 0.346 AC: 5276 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1254 AN: 3468

East Asian (EAS) AF: 0.327 AC: 1695 AN: 5176

South Asian (SAS) AF: 0.238 AC: 1146 AN: 4816

European-Finnish (FIN) AF: 0.327 AC: 3448 AN: 10538

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24887 AN: 67976

Other (OTH) AF: 0.345 AC: 728 AN: 2110

Alfa AF: 0.356 Hom.: 17568

Bravo AF: 0.326

Asia WGS AF: 0.284 AC: 987 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.66
DANN	Benign	0.68
PhyloP100		-0.98
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: rs10513153; hg19: chr5-13770000;