rs201684898

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_181426.2(CCDC39):c.900T>A(p.His300Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000741 in 1,609,198 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. 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. H300N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00076 ( 2 hom. )

Consequence

CCDC39
NM_181426.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:2

Conservation

PhyloP100: -0.732

Publications

4 publications found

Variant links:

Genes affected

CCDC39 (HGNC:25244): (coiled-coil domain 39 molecular ruler complex subunit) The protein encoded by this gene is involved in the motility of cilia and flagella. The encoded protein is essential for the assembly of dynein regulatory and inner dynein arm complexes, which regulate ciliary beat. Defects in this gene are a cause of primary ciliary dyskinesia type 14 (CILD14). [provided by RefSeq, Jul 2011]

CCDC39 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 14
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CCDC39 links:

ENSG00000145075 (HGNC:):

ENSG00000145075 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013421714).

BP6

Variant 3-180654792-A-T is Benign according to our data. Variant chr3-180654792-A-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 262977.

BS2

High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181426.2. 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
	CCDC39	NM_181426.2	MANE Select	c.900T>A	p.His300Gln	missense	Exon 7 of 20	NP_852091.1	Q9UFE4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC39	ENST00000476379.6	TSL:2 MANE Select	c.900T>A	p.His300Gln	missense	Exon 7 of 20	ENSP00000417960.2	Q9UFE4-1
CCDC39	ENST00000936067.1		c.807T>A	p.His269Gln	missense	Exon 6 of 19	ENSP00000606126.1
CCDC39	ENST00000651046.1		c.739-2526T>A		intron	N/A	ENSP00000499175.1	A0A494C1Q3

Frequencies

GnomAD3 genomes

AF:

0.000566

AC:

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000809

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000542

AC:

133

AN:

245530

AF XY:

0.000659

show subpopulations

Gnomad AFR exome

AF:

0.000197

Gnomad AMR exome

AF:

0.000448

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00100

Gnomad OTH exome

AF:

0.000340

GnomAD4 exome

AF:

0.000760

AC:

1107

AN:

1457208

Hom.:

Cov.:

AF XY:

0.000778

AC XY:

564

AN XY:

724824

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33264

American (AMR)

AF:

0.000475

AC:

AN:

44180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26044

East Asian (EAS)

AF:

0.00

AC:

AN:

39396

South Asian (SAS)

AF:

0.000106

AC:

AN:

85308

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53206

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.000902

AC:

1001

AN:

1109886

Other (OTH)

AF:

0.000964

AC:

AN:

60168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

102

153

204

255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000566

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.000620

AC XY:

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.0000966

AC:

AN:

41414

American (AMR)

AF:

0.00131

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0000947

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000809

AC:

AN:

67964

Other (OTH)

AF:

0.00239

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000917

Hom.:

Bravo

AF:

0.000616

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000274

AC:

ESP6500EA

AF:

0.000856

AC:

ExAC

AF:

0.000580

AC:

EpiCase

AF:

0.00105

EpiControl

AF:

0.00114

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia (2)

not provided (1)

not specified (1)

Primary ciliary dyskinesia 14 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.020

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.00045

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.45

M_CAP

Benign

0.028

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.99

PhyloP100

-0.73

PrimateAI

Benign

0.38

PROVEAN

Benign

0.97

REVEL

Benign

0.098

Sift

Benign

0.98

Sift4G

Benign

0.31

Polyphen

0.0040

Vest4

0.19

MutPred

0.20

Gain of glycosylation at T295 (P = 0.048)

MVP

0.38

MPC

0.052

ClinPred

0.0054

GERP RS

-8.0

Varity_R

0.031

Mutation Taster

=98/2

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over