Variant 10-59792934-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 -13 ACMG points.

BP4

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

BP6

Variant 10-59792934-G-T is Benign according to our data. Variant chr10-59792934-G-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
CCDC6	NM_005436.5 linkuse as main transcript	c.1408C>A	p.Pro470Thr	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.1408C>A	p.Pro470Thr	missense_variant	9/9	1	NM_005436.5	ENSP00000263102	P1
CCDC6	ENST00000491922.1 linkuse as main transcript	n.1460C>A		non_coding_transcript_exon_variant	3/3	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

GnomAD3 exomes

AF:

0.511

AC:

126490

AN:

247466

Hom.:

33494

AF XY:

0.511

AC XY:

68238

AN XY:

133520

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 SAS exome

AF:

0.498

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

Gnomad4 AFR exome

AF:

0.256

Gnomad4 AMR exome

AF:

0.636

Gnomad4 ASJ exome

AF:

0.454

Gnomad4 EAS exome

AF:

0.578

Gnomad4 SAS exome

AF:

0.496

Gnomad4 FIN exome

AF:

0.474

Gnomad4 NFE exome

AF:

0.506

Gnomad4 OTH exome

AF:

0.498

GnomAD4 genome

AF:

0.439

AC:

66782

AN:

152052

Hom.:

15707

Cov.:

AF XY:

0.441

AC XY:

32796

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.261

Gnomad4 AMR

AF:

0.532

Gnomad4 ASJ

AF:

0.469

Gnomad4 EAS

AF:

0.609

Gnomad4 SAS

AF:

0.483

Gnomad4 FIN

AF:

0.472

Gnomad4 NFE

AF:

0.504

Gnomad4 OTH

AF:

0.461

Alfa

AF:

0.482

Hom.:

22437

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

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

MutationTaster

Benign

1.8e-7

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.3

REVEL

Benign

0.19

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.16

MPC

0.32

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over