rs113742238

Variant names:

• chr5-13776582-C-A
• rs113742238
• NM_001369.3:c.9230G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-13776582-C-A
• chr5-13776582-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001369.3(DNAH5):​c.9230G>T​(p.Arg3077Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000126 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R3077Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: DNAH5 NM_001369.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:5 B:1
• Conservation: PhyloP100: 6.08
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

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.9230G>T	p.Arg3077Leu	missense	Exon 55 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.9230G>T	p.Arg3077Leu	missense	Exon 55 of 79	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.9185G>T	p.Arg3062Leu	missense	Exon 55 of 79	ENSP00000505288.1	A0A7P0Z455

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152114 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000215 AC: 54 AN: 250916 AF XY: 0.000288

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000127 AC: 186 AN: 1461638 Hom.: 0 Cov.: 33 AF XY: 0.000177 AC XY: 129 AN XY: 727126

African (AFR) AF: 0.0000299 AC: 1 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00108 AC: 93 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5766

European-Non Finnish (NFE) AF: 0.0000666 AC: 74 AN: 1111846

Other (OTH) AF: 0.000166 AC: 10 AN: 60388

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152232 Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7 AN XY: 74448

African (AFR) AF: 0.0000241 AC: 1 AN: 41546

American (AMR) AF: 0.000196 AC: 3 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000268 Hom.: 0

Bravo AF: 0.0000907

ExAC AF: 0.000222 AC: 27

EpiCase AF: 0.000327

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.0032	T
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		6.1
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0010	D
Polyphen		0.99	D
Vest4		0.91
MVP		0.84
MPC		0.33
ClinPred		0.84	D
GERP RS		5.8
Varity_R		0.90
gMVP		0.90
Mutation Taster		=35/65	disease causing

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: rs113742238; hg19: chr5-13776691;