rs61733583

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.2432G>A(p.Arg811His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 1,590,776 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R811C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0051 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 68 hom. )

Consequence

CCDC39
NM_181426.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 3.28

Publications

11 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 links:

TTC14 (HGNC:24697): (tetratricopeptide repeat domain 14) Predicted to enable nucleic acid binding activity. [provided by Alliance of Genome Resources, Apr 2022]

TTC14 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=0.005194932).

BP6

Variant 3-180616670-C-T is Benign according to our data. Variant chr3-180616670-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 162838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00515 (783/152128) while in subpopulation EAS AF = 0.0512 (265/5174). AF 95% confidence interval is 0.0462. There are 9 homozygotes in GnomAd4. There are 404 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 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.2432G>A	p.Arg811His	missense	Exon 18 of 20	NP_852091.1	Q9UFE4-1
	TTC14	NM_001288582.2		c.1775-710C>T		intron	N/A	NP_001275511.1	Q96N46-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC39	ENST00000476379.6	TSL:2 MANE Select	c.2432G>A	p.Arg811His	missense	Exon 18 of 20	ENSP00000417960.2	Q9UFE4-1
TTC14	ENST00000382584.8	TSL:1	c.1775-710C>T		intron	N/A	ENSP00000372027.4	Q96N46-2
CCDC39	ENST00000936067.1		c.2339G>A	p.Arg780His	missense	Exon 17 of 19	ENSP00000606126.1

Frequencies

GnomAD3 genomes

AF:

0.00515

AC:

783

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00768

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.0511

Gnomad SAS

AF:

0.00684

Gnomad FIN

AF:

0.000567

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00376

Gnomad OTH

AF:

0.00479

GnomAD2 exomes

AF:

0.00812

AC:

1741

AN:

214414

AF XY:

0.00803

show subpopulations

Gnomad AFR exome

AF:

0.00144

Gnomad AMR exome

AF:

0.00560

Gnomad ASJ exome

AF:

0.00676

Gnomad EAS exome

AF:

0.0562

Gnomad FIN exome

AF:

0.000603

Gnomad NFE exome

AF:

0.00379

Gnomad OTH exome

AF:

0.00800

GnomAD4 exome

AF:

0.00497

AC:

7153

AN:

1438648

Hom.:

Cov.:

AF XY:

0.00508

AC XY:

3626

AN XY:

713644

show subpopulations

African (AFR)

AF:

0.00160

AC:

AN:

33110

American (AMR)

AF:

0.00572

AC:

236

AN:

41288

Ashkenazi Jewish (ASJ)

AF:

0.00687

AC:

176

AN:

25618

East Asian (EAS)

AF:

0.0440

AC:

1721

AN:

39104

South Asian (SAS)

AF:

0.00677

AC:

566

AN:

83648

European-Finnish (FIN)

AF:

0.000386

AC:

AN:

51838

Middle Eastern (MID)

AF:

0.0180

AC:

103

AN:

5728

European-Non Finnish (NFE)

AF:

0.00349

AC:

3834

AN:

1098856

Other (OTH)

AF:

0.00747

AC:

444

AN:

59458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

330

660

989

1319

1649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

182

364

546

728

910

<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:

0.00515

AC:

783

AN:

152128

Hom.:

Cov.:

AF XY:

0.00543

AC XY:

404

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.00176

AC:

AN:

41510

American (AMR)

AF:

0.00767

AC:

117

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3468

East Asian (EAS)

AF:

0.0512

AC:

265

AN:

5174

South Asian (SAS)

AF:

0.00684

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000567

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00377

AC:

256

AN:

67988

Other (OTH)

AF:

0.00474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

124

165

206

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:

0.00515

Hom.:

Bravo

AF:

0.00602

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00164

AC:

ESP6500EA

AF:

0.00405

AC:

ExAC

AF:

0.00709

AC:

852

Asia WGS

AF:

0.0200

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Primary ciliary dyskinesia (2)

Primary ciliary dyskinesia 14 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.042

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0052

MetaSVM

Benign

-0.38

MutationAssessor

Uncertain

2.6

PhyloP100

3.3

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.39

Sift

Uncertain

0.0050

Sift4G

Benign

0.064

Polyphen

0.99

Vest4

0.43

MVP

0.80

MPC

0.32

ClinPred

0.023

GERP RS

5.1

PromoterAI

-0.0080

Neutral

(source)

Varity_R

0.15

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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