Variant 3-56563777-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001141947.3(CCDC66):c.196A>G(p.Lys66Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000493 in 1,399,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

CCDC66
NM_001141947.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07598981).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC66	NM_001141947.3 linkuse as main transcript	c.196A>G	p.Lys66Glu	missense_variant	4/18	ENST00000394672.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC66	ENST00000394672.8 linkuse as main transcript	c.196A>G	p.Lys66Glu	missense_variant	4/18	1	NM_001141947.3	A2	A2RUB6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000314

AC:

AN:

159272

Hom.:

AF XY:

0.0000358

AC XY:

AN XY:

83888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000808

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000493

AC:

AN:

1399586

Hom.:

Cov.:

AF XY:

0.0000565

AC XY:

AN XY:

690322

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000630

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000151

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2022

The c.196A>G (p.K66E) alteration is located in exon 4 (coding exon 4) of the CCDC66 gene. This alteration results from a A to G substitution at nucleotide position 196, causing the lysine (K) at amino acid position 66 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Benign

0.40

DEOGEN2

Benign

0.024

T;T;.

Eigen

Benign

0.13

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.076

T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.97

N;N;N

REVEL

Benign

0.091

Sift

Benign

0.62

T;T;T

Sift4G

Benign

0.57

T;T;T

Polyphen

0.83

.;P;.

Vest4

0.16, 0.16

MutPred

0.17

Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);.;

MVP

0.24

MPC

0.017

ClinPred

0.15

GERP RS

5.9

Varity_R

0.15

gMVP

0.061

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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