rs30175

Variant names:

• chr5-13714631-G-A
• rs30175
• NM_001369.3:c.12910-11C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-13714631-G-A
• chr5-13714631-G-C

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.12910-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,612,616 control chromosomes in the GnomAD database, including 137,296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11943 hom., cov: 32)
  • Exomes 𝑓: 0.41 (125353 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Scores: Splicing: ADA: 0.00001917
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.717
• Publications: 9 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=-0.9).
• BP6: Variant 5-13714631-G-A is Benign according to our data. Variant chr5-13714631-G-A is described in ClinVar as Benign. ClinVar VariationId is 163133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.435 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.12910-11C>T		intron	N/A	NP_001360.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.12910-11C>T		intron	N/A	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.12865-11C>T		intron	N/A	ENSP00000505288.1
	DNAH5	ENST00000683611.1		n.232C>T		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59889 AN: 151896 Hom.: 11928 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.399

GnomAD2 exomes AF: 0.411 AC: 102830 AN: 250040 AF XY: 0.414

Gnomad AFR exome AF: 0.367

Gnomad AMR exome AF: 0.439

Gnomad ASJ exome AF: 0.416

Gnomad EAS exome AF: 0.412

Gnomad FIN exome AF: 0.326

Gnomad NFE exome AF: 0.413

Gnomad OTH exome AF: 0.415

GnomAD4 exome AF: 0.413 AC: 603156 AN: 1460600 Hom.: 125353 Cov.: 36 AF XY: 0.414 AC XY: 300768 AN XY: 726608

African (AFR) AF: 0.358 AC: 11981 AN: 33452

American (AMR) AF: 0.434 AC: 19363 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 10602 AN: 26136

East Asian (EAS) AF: 0.400 AC: 15860 AN: 39638

South Asian (SAS) AF: 0.453 AC: 39074 AN: 86200

European-Finnish (FIN) AF: 0.331 AC: 17677 AN: 53364

Middle Eastern (MID) AF: 0.443 AC: 2391 AN: 5402

European-Non Finnish (NFE) AF: 0.415 AC: 461246 AN: 1111440

Other (OTH) AF: 0.414 AC: 24962 AN: 60324

GnomAD4 genome AF: 0.394 AC: 59950 AN: 152016 Hom.: 11943 Cov.: 32 AF XY: 0.390 AC XY: 28945 AN XY: 74294

African (AFR) AF: 0.367 AC: 15215 AN: 41450

American (AMR) AF: 0.410 AC: 6269 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1428 AN: 3470

East Asian (EAS) AF: 0.431 AC: 2224 AN: 5162

South Asian (SAS) AF: 0.450 AC: 2171 AN: 4820

European-Finnish (FIN) AF: 0.316 AC: 3340 AN: 10566

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27928 AN: 67956

Other (OTH) AF: 0.402 AC: 848 AN: 2110

Alfa AF: 0.403 Hom.: 17883

Bravo AF: 0.400

Asia WGS AF: 0.447 AC: 1556 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Primary ciliary dyskinesia 3 (3)
-	-	2	not provided (2)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.48
PhyloP100		0.72
Mutation Taster		=30/70	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000019
dbscSNV1_RF	Benign	0.0
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: rs30175; hg19: chr5-13714740; COSMIC: COSV54214344;