3-180659682-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_181426.2(CCDC39):c.604G>A(p.Ala202Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,608,360 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A202A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.010 ( 17 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 28 hom. )

Consequence

CCDC39
NM_181426.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 3.15

Publications

6 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, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008814514).

BP6

Variant 3-180659682-C-T is Benign according to our data. Variant chr3-180659682-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0101 (1533/152218) while in subpopulation AFR AF = 0.0346 (1438/41544). AF 95% confidence interval is 0.0331. There are 17 homozygotes in GnomAd4. There are 682 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 17 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.604G>A	p.Ala202Thr	missense	Exon 5 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.604G>A	p.Ala202Thr	missense	Exon 5 of 20	ENSP00000417960.2	Q9UFE4-1
CCDC39	ENST00000651046.1		c.604G>A	p.Ala202Thr	missense	Exon 5 of 19	ENSP00000499175.1	A0A494C1Q3
CCDC39	ENST00000936067.1		c.517-102G>A		intron	N/A	ENSP00000606126.1

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1529

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0347

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00413

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00911

GnomAD2 exomes

AF:

0.00252

AC:

614

AN:

244108

AF XY:

0.00167

show subpopulations

Gnomad AFR exome

AF:

0.0362

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000987

Gnomad OTH exome

AF:

0.000847

GnomAD4 exome

AF:

0.00106

AC:

1540

AN:

1456142

Hom.:

Cov.:

AF XY:

0.000889

AC XY:

644

AN XY:

724196

show subpopulations

African (AFR)

AF:

0.0380

AC:

1258

AN:

33084

American (AMR)

AF:

0.00160

AC:

AN:

43720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25904

East Asian (EAS)

AF:

0.00

AC:

AN:

39544

South Asian (SAS)

AF:

0.000153

AC:

AN:

84818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53130

Middle Eastern (MID)

AF:

0.000698

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.0000414

AC:

AN:

1110116

Other (OTH)

AF:

0.00248

AC:

149

AN:

60098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

138

207

276

345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.0101

AC:

1533

AN:

152218

Hom.:

Cov.:

AF XY:

0.00916

AC XY:

682

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0346

AC:

1438

AN:

41544

American (AMR)

AF:

0.00426

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67998

Other (OTH)

AF:

0.00901

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

168

251

335

419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00326

Hom.:

Bravo

AF:

0.0122

ESP6500AA

AF:

0.0390

AC:

142

ESP6500EA

AF:

0.000368

AC:

ExAC

AF:

0.00309

AC:

373

Asia WGS

AF:

0.00115

AC:

AN:

3476

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Primary ciliary dyskinesia (2)

Primary ciliary dyskinesia 14 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0088

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

PhyloP100

3.1

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.16

Sift

Uncertain

0.0090

Sift4G

Benign

0.27

Polyphen

1.0

Vest4

0.24

MVP

0.55

MPC

0.070

ClinPred

0.036

GERP RS

5.9

Varity_R

0.18

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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