Genetic Variant ENST00000326595:c.-29A>C (chr3-56558908-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000326595.11(CCDC66):c.-29A>C 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 0.00000144 in 1,390,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CCDC66
ENST00000326595.11 5_prime_UTR_premature_start_codon_gain

Scores

Splicing: ADA: 0.0008216

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0980

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13800177).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000326595.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC66	NM_001141947.3	MANE Select	c.74A>C	p.Tyr25Ser	missense splice_region	Exon 2 of 18	NP_001135419.1	A2RUB6-1
CCDC66	NM_001012506.5		c.-29A>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 18	NP_001012524.4	A2RUB6-3
CCDC66	NM_001353152.1		c.-180A>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 19	NP_001340081.1	A2RUB6-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC66	ENST00000326595.11	TSL:1	c.-29A>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 18	ENSP00000326050.7	A2RUB6-3
CCDC66	ENST00000394672.8	TSL:1 MANE Select	c.74A>C	p.Tyr25Ser	missense splice_region	Exon 2 of 18	ENSP00000378167.3	A2RUB6-1
CCDC66	ENST00000326595.11	TSL:1	c.-29A>C		splice_region	Exon 2 of 18	ENSP00000326050.7	A2RUB6-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1390526

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

686220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31388

American (AMR)

AF:

0.00

AC:

AN:

35376

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25060

East Asian (EAS)

AF:

0.00

AC:

AN:

35528

South Asian (SAS)

AF:

0.00

AC:

AN:

78478

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48996

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5612

European-Non Finnish (NFE)

AF:

0.00000186

AC:

AN:

1072420

Other (OTH)

AF:

0.00

AC:

AN:

57668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.028

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.14

MetaSVM

Pathogenic

0.84

MutationAssessor

Benign

1.8

PhyloP100

-0.098

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.41

Sift

Benign

0.19

Sift4G

Benign

0.39

Polyphen

0.041

Vest4

0.26

MutPred

0.22

Gain of disorder (P = 0.0063)

MVP

0.58

MPC

0.018

ClinPred

0.092

GERP RS

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.23

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00082

dbscSNV1_RF

Benign

0.15

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over