Variant 10-59793005-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000263102.7(CCDC6):c.1337C>T(p.Pro446Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00937 in 1,612,752 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0066 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0097 ( 86 hom. )

Consequence

CCDC6
ENST00000263102.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.60

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046695173).

BP6

Variant 10-59793005-G-A is Benign according to our data. Variant chr10-59793005-G-A is described in ClinVar as [Benign]. Clinvar id is 3024687.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1000 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC6	NM_005436.5 linkuse as main transcript	c.1337C>T	p.Pro446Leu	missense_variant	9/9	ENST00000263102.7	NP_005427.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC6	ENST00000263102.7 linkuse as main transcript	c.1337C>T	p.Pro446Leu	missense_variant	9/9	1	NM_005436.5	ENSP00000263102	P1
CCDC6	ENST00000491922.1 linkuse as main transcript	n.1389C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00660

AC:

1001

AN:

151626

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00208

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00672

AC:

1675

AN:

249408

Hom.:

AF XY:

0.00679

AC XY:

916

AN XY:

134818

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00321

Gnomad ASJ exome

AF:

0.0111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000624

Gnomad FIN exome

AF:

0.00205

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.00624

GnomAD4 exome

AF:

0.00966

AC:

14115

AN:

1461008

Hom.:

Cov.:

AF XY:

0.00944

AC XY:

6861

AN XY:

726788

show subpopulations

Gnomad4 AFR exome

AF:

0.00182

Gnomad4 AMR exome

AF:

0.00318

Gnomad4 ASJ exome

AF:

0.0114

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000568

Gnomad4 FIN exome

AF:

0.00262

Gnomad4 NFE exome

AF:

0.0117

Gnomad4 OTH exome

AF:

0.00744

GnomAD4 genome

AF:

0.00659

AC:

1000

AN:

151744

Hom.:

Cov.:

AF XY:

0.00586

AC XY:

435

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00208

Gnomad4 NFE

AF:

0.0115

Gnomad4 OTH

AF:

0.00997

Alfa

AF:

0.0104

Hom.:

Bravo

AF:

0.00646

TwinsUK

AF:

0.0146

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0113

AC:

ExAC

AF:

0.00705

AC:

855

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0103

EpiControl

AF:

0.00906

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

CCDC6: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.0

REVEL

Benign

0.038

Sift

Benign

0.049

Sift4G

Uncertain

0.0060

Polyphen

0.014

Vest4

0.30

MVP

0.093

MPC

0.30

ClinPred

0.028

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.081

gMVP

0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over