Genetic Variant CCDC6:p.Ile366Val (chr10-59804429-T-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_005436.5(CCDC6):c.1096A>G(p.Ile366Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000055 in 1,453,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I366L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CCDC6
NM_005436.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.01

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2934472).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005436.5. 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
	CCDC6	NM_005436.5	MANE Select	c.1096A>G	p.Ile366Val	missense	Exon 7 of 9	NP_005427.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC6	ENST00000263102.7	TSL:1 MANE Select	c.1096A>G	p.Ile366Val	missense	Exon 7 of 9	ENSP00000263102.6	Q16204
CCDC6	ENST00000862752.1		c.1090A>G	p.Ile364Val	missense	Exon 7 of 9	ENSP00000532811.1
CCDC6	ENST00000936420.1		c.1090A>G	p.Ile364Val	missense	Exon 7 of 9	ENSP00000606479.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000797

AC:

AN:

250924

AF XY:

0.00000738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000550

AC:

AN:

1453864

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723830

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33286

American (AMR)

AF:

0.0000224

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86086

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00000543

AC:

AN:

1104766

Other (OTH)

AF:

0.00

AC:

AN:

60112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.016

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.81

PhyloP100

8.0

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.43

REVEL

Benign

0.16

Sift

Benign

0.24

Sift4G

Benign

0.58

Polyphen

0.52

Vest4

0.41

MutPred

0.20

Loss of catalytic residue at P368 (P = 0.0368)

MVP

0.23

MPC

0.28

ClinPred

0.39

GERP RS

5.5

Varity_R

0.081

gMVP

0.46

Mutation Taster

=73/27

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over