rs79386936

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.2278A>G(p.Thr760Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,412,530 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T760T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0094 ( 27 hom., cov: 32)

Exomes 𝑓: 0.00084 ( 26 hom. )

Consequence

CCDC39
NM_181426.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.39

Publications

1 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=0.0025066435).

BP6

Variant 3-180616954-T-C is Benign according to our data. Variant chr3-180616954-T-C is described in ClinVar as Benign. ClinVar VariationId is 226484.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 = 0.00943 (1437/152344) while in subpopulation AFR AF = 0.0332 (1379/41578). AF 95% confidence interval is 0.0317. There are 27 homozygotes in GnomAd4. There are 667 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 27 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.2278A>G	p.Thr760Ala	missense	Exon 17 of 20	NP_852091.1	Q9UFE4-1
	TTC14	NM_001288582.2		c.1775-426T>C		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.2278A>G	p.Thr760Ala	missense	Exon 17 of 20	ENSP00000417960.2	Q9UFE4-1
TTC14	ENST00000382584.8	TSL:1	c.1775-426T>C		intron	N/A	ENSP00000372027.4	Q96N46-2
CCDC39	ENST00000936067.1		c.2185A>G	p.Thr729Ala	missense	Exon 16 of 19	ENSP00000606126.1

Frequencies

GnomAD3 genomes

AF:

0.00943

AC:

1436

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0332

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00270

AC:

456

AN:

168884

AF XY:

0.00222

show subpopulations

Gnomad AFR exome

AF:

0.0366

Gnomad AMR exome

AF:

0.00170

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000776

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000532

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.000836

AC:

1054

AN:

1260186

Hom.:

Cov.:

AF XY:

0.000771

AC XY:

484

AN XY:

627734

show subpopulations

African (AFR)

AF:

0.0319

AC:

881

AN:

27592

American (AMR)

AF:

0.00159

AC:

AN:

32666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23672

East Asian (EAS)

AF:

0.0000266

AC:

AN:

37570

South Asian (SAS)

AF:

0.000112

AC:

AN:

71698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48766

Middle Eastern (MID)

AF:

0.00114

AC:

AN:

5270

European-Non Finnish (NFE)

AF:

0.0000115

AC:

AN:

959812

Other (OTH)

AF:

0.00179

AC:

AN:

53140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

141

188

235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00943

AC:

1437

AN:

152344

Hom.:

Cov.:

AF XY:

0.00895

AC XY:

667

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0332

AC:

1379

AN:

41578

American (AMR)

AF:

0.00294

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

147

221

294

368

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:

0.00353

Hom.:

Bravo

AF:

0.0111

ESP6500AA

AF:

0.0344

AC:

123

ESP6500EA

AF:

0.000124

AC:

ExAC

AF:

0.00304

AC:

362

Asia WGS

AF:

0.00231

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Primary ciliary dyskinesia (2)

not provided (1)

Primary ciliary dyskinesia 14 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0036

Eigen

Benign

0.060

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.62

MetaRNN

Benign

0.0025

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.7

PhyloP100

1.4

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.77

REVEL

Benign

0.26

Sift

Benign

0.21

Sift4G

Benign

0.26

Polyphen

0.82

Vest4

0.35

MVP

0.68

MPC

0.090

ClinPred

0.0067

GERP RS

4.8

PromoterAI

0.0017

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.085

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