Genetic Variant CCDC6:p.Pro470Thr (chr10-59792934-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005436.5(CCDC6):c.1408C>A(p.Pro470Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.497 in 1,609,104 control chromosomes in the GnomAD database, including 202,591 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.44 ( 15707 hom., cov: 33)

Exomes 𝑓: 0.50 ( 186884 hom. )

Consequence

CCDC6
NM_005436.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.95

Publications

47 publications found

Variant links:

Genes affected

CCDC6 (HGNC:18782): (coiled-coil domain containing 6) This gene encodes a coiled-coil domain-containing protein. The encoded protein is ubiquitously expressed and may function as a tumor suppressor. A chromosomal rearrangement resulting in the expression of a fusion gene containing a portion of this gene and the intracellular kinase-encoding domain of the ret proto-oncogene is the cause of thyroid papillary carcinoma.[provided by RefSeq, Sep 2010]

CCDC6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.9169785E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC6	NM_005436.5 link	c.1408C>A	p.Pro470Thr	missense_variant	Exon 9 of 9	ENST00000263102.7	NP_005427.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC6	ENST00000263102.7 link	c.1408C>A	p.Pro470Thr	missense_variant	Exon 9 of 9	1	NM_005436.5	ENSP00000263102.6
CCDC6	ENST00000491922.1 link	n.1460C>A		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

66756

AN:

151932

Hom.:

15693

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.408

Gnomad AMR

AF:

0.531

Gnomad ASJ

AF:

0.469

Gnomad EAS

AF:

0.610

Gnomad SAS

AF:

0.482

Gnomad FIN

AF:

0.472

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.460

GnomAD2 exomes

AF:

0.511

AC:

126490

AN:

247466

AF XY:

0.511

show subpopulations

Gnomad AFR exome

AF:

0.253

Gnomad AMR exome

AF:

0.647

Gnomad ASJ exome

AF:

0.455

Gnomad EAS exome

AF:

0.607

Gnomad FIN exome

AF:

0.479

Gnomad NFE exome

AF:

0.506

Gnomad OTH exome

AF:

0.505

GnomAD4 exome

AF:

0.503

AC:

733356

AN:

1457052

Hom.:

186884

Cov.:

AF XY:

0.504

AC XY:

364974

AN XY:

724300

show subpopulations

African (AFR)

AF:

0.256

AC:

8549

AN:

33412

American (AMR)

AF:

0.636

AC:

28278

AN:

44490

Ashkenazi Jewish (ASJ)

AF:

0.454

AC:

11661

AN:

25706

East Asian (EAS)

AF:

0.578

AC:

22912

AN:

39672

South Asian (SAS)

AF:

0.496

AC:

42350

AN:

85356

European-Finnish (FIN)

AF:

0.474

AC:

25198

AN:

53146

Middle Eastern (MID)

AF:

0.506

AC:

2897

AN:

5722

European-Non Finnish (NFE)

AF:

0.506

AC:

561541

AN:

1109336

Other (OTH)

AF:

0.498

AC:

29970

AN:

60212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

18873

37747

56620

75494

94367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16294

32588

48882

65176

81470

<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:

0.439

AC:

66782

AN:

152052

Hom.:

15707

Cov.:

AF XY:

0.441

AC XY:

32796

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.261

AC:

10827

AN:

41472

American (AMR)

AF:

0.532

AC:

8127

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.469

AC:

1628

AN:

3470

East Asian (EAS)

AF:

0.609

AC:

3151

AN:

5172

South Asian (SAS)

AF:

0.483

AC:

2324

AN:

4812

European-Finnish (FIN)

AF:

0.472

AC:

4981

AN:

10556

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.504

AC:

34242

AN:

67964

Other (OTH)

AF:

0.461

AC:

976

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1863

3726

5589

7452

9315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

632

1264

1896

2528

3160

<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:

0.471

Hom.:

36111

Bravo

AF:

0.440

TwinsUK

AF:

0.505

AC:

1874

ALSPAC

AF:

0.502

AC:

1935

ESP6500AA

AF:

0.264

AC:

1164

ESP6500EA

AF:

0.503

AC:

4329

ExAC

AF:

0.500

AC:

60692

Asia WGS

AF:

0.483

AC:

1679

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.067

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.70

MetaRNN

Benign

0.000089

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.81

PhyloP100

8.9

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.3

REVEL

Benign

0.19

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.16

ClinPred

0.050

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.18

Mutation Taster

=77/23

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over