rs10041113

Variant names:

• chr5-13844936-G-A
• rs10041113
• NM_001369.3:c.5172C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-13844936-G-A
• chr5-13844936-G-C
• chr5-13844936-G-T

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.5172C>T​(p.Ala1724Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,613,462 control chromosomes in the GnomAD database, including 108,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12599 hom., cov: 32)
  • Exomes 𝑓: 0.36 (95960 hom.)
• Consequence: DNAH5 NM_001369.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.323
• Publications: 12 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=-0.55).
• BP6: Variant 5-13844936-G-A is Benign according to our data. Variant chr5-13844936-G-A is described in ClinVar as Benign. ClinVar VariationId is 178749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.323 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 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.5172C>T	p.Ala1724Ala	synonymous	Exon 32 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.5172C>T	p.Ala1724Ala	synonymous	Exon 32 of 79	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.5127C>T	p.Ala1709Ala	synonymous	Exon 32 of 79	ENSP00000505288.1	A0A7P0Z455

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60839 AN: 151816 Hom.: 12580 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.400

GnomAD2 exomes AF: 0.379 AC: 95236 AN: 251394 AF XY: 0.372

Gnomad AFR exome AF: 0.502

Gnomad AMR exome AF: 0.362

Gnomad ASJ exome AF: 0.341

Gnomad EAS exome AF: 0.630

Gnomad FIN exome AF: 0.320

Gnomad NFE exome AF: 0.351

Gnomad OTH exome AF: 0.368

GnomAD4 exome AF: 0.359 AC: 524914 AN: 1461526 Hom.: 95960 Cov.: 40 AF XY: 0.358 AC XY: 259994 AN XY: 727102

African (AFR) AF: 0.497 AC: 16643 AN: 33466

American (AMR) AF: 0.368 AC: 16479 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 8858 AN: 26134

East Asian (EAS) AF: 0.559 AC: 22180 AN: 39698

South Asian (SAS) AF: 0.339 AC: 29210 AN: 86252

European-Finnish (FIN) AF: 0.326 AC: 17441 AN: 53420

Middle Eastern (MID) AF: 0.305 AC: 1758 AN: 5762

European-Non Finnish (NFE) AF: 0.351 AC: 389973 AN: 1111694

Other (OTH) AF: 0.371 AC: 22372 AN: 60378

GnomAD4 genome AF: 0.401 AC: 60900 AN: 151936 Hom.: 12599 Cov.: 32 AF XY: 0.398 AC XY: 29530 AN XY: 74266

African (AFR) AF: 0.499 AC: 20662 AN: 41408

American (AMR) AF: 0.371 AC: 5670 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1204 AN: 3472

East Asian (EAS) AF: 0.606 AC: 3116 AN: 5138

South Asian (SAS) AF: 0.345 AC: 1667 AN: 4826

European-Finnish (FIN) AF: 0.316 AC: 3334 AN: 10550

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23947 AN: 67968

Other (OTH) AF: 0.397 AC: 835 AN: 2102

Alfa AF: 0.371 Hom.: 8321

Bravo AF: 0.413

Asia WGS AF: 0.454 AC: 1578 AN: 3478

EpiCase AF: 0.349

EpiControl AF: 0.345

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)
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia 3 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.9
DANN	Benign	0.52
PhyloP100		-0.32
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10041113; hg19: chr5-13845045; COSMIC: COSV54225156;