rs12655133

Variant names:

• chr5-13769148-T-A
• rs12655133
• NM_001369.3:c.9721-12A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-13769148-T-A
• chr5-13769148-T-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.9721-12A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,612,898 control chromosomes in the GnomAD database, including 103,426 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9292 hom., cov: 33)
  • Exomes 𝑓: 0.36 (94134 hom.)
• Consequence: DNAH5 NM_001369.3 intron
• Scores: Splicing: ADA: 0.00001179
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -2.82
• 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: 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=-0.9).
• BP6: Variant 5-13769148-T-A is Benign according to our data. Variant chr5-13769148-T-A is described in ClinVar as Benign. ClinVar VariationId is 167003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.363 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.9721-12A>T		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.9721-12A>T		intron	N/A	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.9676-12A>T		intron	N/A	ENSP00000505288.1	A0A7P0Z455
	DNAH5	ENST00000504001.3	TSL:5	n.433-12A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52965 AN: 151936 Hom.: 9288 Cov.: 33

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.362

GnomAD2 exomes AF: 0.339 AC: 85137 AN: 250844 AF XY: 0.338

Gnomad AFR exome AF: 0.330

Gnomad AMR exome AF: 0.328

Gnomad ASJ exome AF: 0.375

Gnomad EAS exome AF: 0.322

Gnomad FIN exome AF: 0.336

Gnomad NFE exome AF: 0.368

Gnomad OTH exome AF: 0.372

GnomAD4 exome AF: 0.357 AC: 520957 AN: 1460844 Hom.: 94134 Cov.: 35 AF XY: 0.353 AC XY: 256535 AN XY: 726840

African (AFR) AF: 0.339 AC: 11348 AN: 33464

American (AMR) AF: 0.333 AC: 14891 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 9714 AN: 26130

East Asian (EAS) AF: 0.323 AC: 12813 AN: 39696

South Asian (SAS) AF: 0.246 AC: 21182 AN: 86240

European-Finnish (FIN) AF: 0.338 AC: 17975 AN: 53234

Middle Eastern (MID) AF: 0.413 AC: 2380 AN: 5762

European-Non Finnish (NFE) AF: 0.368 AC: 408699 AN: 1111246

Other (OTH) AF: 0.364 AC: 21955 AN: 60358

GnomAD4 genome AF: 0.348 AC: 52985 AN: 152054 Hom.: 9292 Cov.: 33 AF XY: 0.347 AC XY: 25745 AN XY: 74300

African (AFR) AF: 0.332 AC: 13787 AN: 41498

American (AMR) AF: 0.356 AC: 5424 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1255 AN: 3472

East Asian (EAS) AF: 0.332 AC: 1713 AN: 5166

South Asian (SAS) AF: 0.238 AC: 1150 AN: 4824

European-Finnish (FIN) AF: 0.326 AC: 3441 AN: 10542

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24924 AN: 67984

Other (OTH) AF: 0.360 AC: 759 AN: 2106

Alfa AF: 0.276 Hom.: 1023

Bravo AF: 0.354

Asia WGS AF: 0.292 AC: 1015 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	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	0.056
DANN	Benign	0.25
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000012
dbscSNV1_RF	Benign	0.044
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: rs12655133; hg19: chr5-13769257; COSMIC: COSV54227247;