Variant chr3-56594003-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001141947.3(CCDC66):c.1379G>A(p.Arg460Gln) variant causes a missense change. The variant allele was found at a frequency of 0.472 in 1,612,838 control chromosomes in the GnomAD database, including 194,875 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.38 ( 13692 hom., cov: 32)

Exomes 𝑓: 0.48 ( 181183 hom. )

Consequence

CCDC66
NM_001141947.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.16

Variant links:

Genes affected

CCDC66 (HGNC:27709): (coiled-coil domain containing 66) Enables microtubule binding activity. Involved in cilium assembly; microtubule bundle formation; and regulation of protein localization to cilium. Located in several cellular components, including Flemming body; microtubule cytoskeleton; and photoreceptor inner segment. [provided by Alliance of Genome Resources, Apr 2022]

CCDC66 links:

CCDC66 (HGNC:):

CCDC66 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.8731775E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC66	NM_001141947.3 linkuse as main transcript	c.1379G>A	p.Arg460Gln	missense_variant	10/18	ENST00000394672.8	NP_001135419.1	A2RUB6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC66	ENST00000394672.8 linkuse as main transcript	c.1379G>A	p.Arg460Gln	missense_variant	10/18	1	NM_001141947.3	ENSP00000378167.3		A2RUB6-1

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

58105

AN:

151888

Hom.:

13695

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.428

Gnomad AMR

AF:

0.320

Gnomad ASJ

AF:

0.581

Gnomad EAS

AF:

0.0433

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.505

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.542

Gnomad OTH

AF:

0.374

GnomAD3 exomes

AF:

0.393

AC:

98833

AN:

251334

Hom.:

23834

AF XY:

0.401

AC XY:

54454

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.144

Gnomad AMR exome

AF:

0.224

Gnomad ASJ exome

AF:

0.561

Gnomad EAS exome

AF:

0.0360

Gnomad SAS exome

AF:

0.247

Gnomad FIN exome

AF:

0.511

Gnomad NFE exome

AF:

0.537

Gnomad OTH exome

AF:

0.454

GnomAD4 exome

AF:

0.482

AC:

703667

AN:

1460830

Hom.:

181183

Cov.:

AF XY:

0.478

AC XY:

347733

AN XY:

726786

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.237

Gnomad4 ASJ exome

AF:

0.561

Gnomad4 EAS exome

AF:

0.0681

Gnomad4 SAS exome

AF:

0.252

Gnomad4 FIN exome

AF:

0.516

Gnomad4 NFE exome

AF:

0.533

Gnomad4 OTH exome

AF:

0.442

GnomAD4 genome

AF:

0.382

AC:

58091

AN:

152008

Hom.:

13692

Cov.:

AF XY:

0.376

AC XY:

27922

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.319

Gnomad4 ASJ

AF:

0.581

Gnomad4 EAS

AF:

0.0436

Gnomad4 SAS

AF:

0.231

Gnomad4 FIN

AF:

0.505

Gnomad4 NFE

AF:

0.542

Gnomad4 OTH

AF:

0.370

Alfa

AF:

0.493

Hom.:

48037

Bravo

AF:

0.357

TwinsUK

AF:

0.537

AC:

1991

ALSPAC

AF:

0.549

AC:

2115

ESP6500AA

AF:

0.154

AC:

678

ESP6500EA

AF:

0.537

AC:

4621

ExAC

AF:

0.396

AC:

48100

Asia WGS

AF:

0.144

AC:

504

AN:

3478

EpiCase

AF:

0.543

EpiControl

AF:

0.535

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.077

T;T;.

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

D;D;D

MetaRNN

Benign

0.00079

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.3

.;M;.

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Benign

0.20

Sift

Benign

0.037

D;T;T

Sift4G

Benign

0.12

T;T;T

Polyphen

1.0

.;D;.

Vest4

0.27, 0.38

MPC

0.12

ClinPred

0.019

GERP RS

5.8

Varity_R

0.26

gMVP

0.11

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

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