chr3-180647173-T-C

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.1433A>G(p.Gln478Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00554 in 1,612,170 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 37 hom. )

Consequence

CCDC39
NM_181426.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.77

Publications

7 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003198415).

BP6

Variant 3-180647173-T-C is Benign according to our data. Variant chr3-180647173-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00309 (471/152196) while in subpopulation NFE AF = 0.00561 (381/67956). AF 95% confidence interval is 0.00514. There are 2 homozygotes in GnomAd4. There are 201 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR,AD 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.1433A>G	p.Gln478Arg	missense	Exon 11 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.1433A>G	p.Gln478Arg	missense	Exon 11 of 20	ENSP00000417960.2	Q9UFE4-1
CCDC39	ENST00000936067.1		c.1340A>G	p.Gln447Arg	missense	Exon 10 of 19	ENSP00000606126.1
CCDC39	ENST00000651046.1		c.1241A>G	p.Gln414Arg	missense	Exon 10 of 19	ENSP00000499175.1	A0A494C1Q3

Frequencies

GnomAD3 genomes

AF:

0.00310

AC:

471

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000722

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00562

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00285

AC:

705

AN:

247522

AF XY:

0.00296

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.000555

Gnomad ASJ exome

AF:

0.00449

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000513

Gnomad NFE exome

AF:

0.00500

Gnomad OTH exome

AF:

0.00200

GnomAD4 exome

AF:

0.00579

AC:

8454

AN:

1459974

Hom.:

Cov.:

AF XY:

0.00556

AC XY:

4040

AN XY:

726200

show subpopulations

African (AFR)

AF:

0.000718

AC:

AN:

33420

American (AMR)

AF:

0.000650

AC:

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.00479

AC:

125

AN:

26096

East Asian (EAS)

AF:

0.00

AC:

AN:

39562

South Asian (SAS)

AF:

0.00161

AC:

138

AN:

85864

European-Finnish (FIN)

AF:

0.000451

AC:

AN:

53236

Middle Eastern (MID)

AF:

0.000521

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00695

AC:

7720

AN:

1111144

Other (OTH)

AF:

0.00649

AC:

391

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

391

782

1173

1564

1955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.00309

AC:

471

AN:

152196

Hom.:

Cov.:

AF XY:

0.00270

AC XY:

201

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.00118

AC:

AN:

41562

American (AMR)

AF:

0.000721

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00547

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00104

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00561

AC:

381

AN:

67956

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00463

Hom.:

Bravo

AF:

0.00303

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00168

AC:

ESP6500EA

AF:

0.00567

AC:

ExAC

AF:

0.00273

AC:

330

Asia WGS

AF:

0.00144

AC:

AN:

3476

EpiCase

AF:

0.00453

EpiControl

AF:

0.00499

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (3)

Primary ciliary dyskinesia (2)

Primary ciliary dyskinesia 14 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.00068

Eigen

Benign

0.078

Eigen_PC

Benign

0.097

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.74

M_CAP

Benign

0.0092

MetaRNN

Benign

0.0032

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PhyloP100

1.8

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.28

REVEL

Benign

0.032

Sift

Benign

0.069

Sift4G

Benign

0.34

Polyphen

0.93

Vest4

0.13

MVP

0.50

MPC

0.066

ClinPred

0.026

GERP RS

2.8

Varity_R

0.071

Mutation Taster

=100/0

polymorphism

(source)

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

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