Genetic Variant ENST00000326595:c.-33C>G (chr3-56558904-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The ENST00000326595(CCDC66):c.-33C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,391,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

CCDC66
ENST00000326595 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.244

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:

Genome browser will be placed here

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=0.21467191).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC66	NM_001141947.3 link	c.70C>G	p.Pro24Ala	missense_variant	Exon 2 of 18	ENST00000394672.8	NP_001135419.1	A2RUB6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC66	ENST00000394672.8 link	c.70C>G	p.Pro24Ala	missense_variant	Exon 2 of 18	1	NM_001141947.3	ENSP00000378167.3		A2RUB6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.19e-7

AC:

AN:

1391404

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

686646

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:

9.32e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.70C>G (p.P24A) alteration is located in exon 2 (coding exon 2) of the CCDC66 gene. This alteration results from a C to G substitution at nucleotide position 70, causing the proline (P) at amino acid position 24 to be replaced by an alanine (A). 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

0.13

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.034

T;T

Eigen

Benign

0.047

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.74

T;T

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.21

T;T

MetaSVM

Uncertain

0.79

MutationAssessor

Benign

2.0

.;M

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.9

N;N

REVEL

Uncertain

0.41

Sift

Benign

0.25

T;T

Sift4G

Benign

0.71

T;T

Polyphen

0.21

.;B

Vest4

0.13

MutPred

0.36

Gain of MoRF binding (P = 0.0436);Gain of MoRF binding (P = 0.0436);

MVP

0.58

MPC

0.12

ClinPred

0.46

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.070

gMVP

0.12

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over