3-56621581-C-T

Variant names:

Variant summary

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

The NM_001141947.3(CCDC66):c.2810C>T(p.Ala937Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,601,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

CCDC66
NM_001141947.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.898

Publications

7 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:

TASOR (HGNC:30314): (transcription activation suppressor) Enables chromatin binding activity. Involved in negative regulation of single stranded viral RNA replication via double stranded DNA intermediate; protein localization to heterochromatin; and regulation of gene expression. Located in heterochromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TASOR 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=0.092132956).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001141947.3. 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.2810C>T	p.Ala937Val	missense	Exon 18 of 18	NP_001135419.1	A2RUB6-1
TASOR	NM_001365635.2	MANE Select	c.*1456G>A		3_prime_UTR	Exon 24 of 24	NP_001352564.1	Q9UK61-1
CCDC66	NM_001353147.1		c.2828C>T	p.Ala943Val	missense	Exon 18 of 18	NP_001340076.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC66	ENST00000394672.8	TSL:1 MANE Select	c.2810C>T	p.Ala937Val	missense	Exon 18 of 18	ENSP00000378167.3	A2RUB6-1
CCDC66	ENST00000326595.11	TSL:1	c.2708C>T	p.Ala903Val	missense	Exon 18 of 18	ENSP00000326050.7	A2RUB6-3
TASOR	ENST00000683822.1	MANE Select	c.*1456G>A		3_prime_UTR	Exon 24 of 24	ENSP00000508241.1	Q9UK61-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000369

AC:

AN:

243724

AF XY:

0.0000379

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000714

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000200

AC:

AN:

1448960

Hom.:

Cov.:

AF XY:

0.0000277

AC XY:

AN XY:

720734

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33024

American (AMR)

AF:

0.00

AC:

AN:

42254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25786

East Asian (EAS)

AF:

0.00

AC:

AN:

39372

South Asian (SAS)

AF:

0.00

AC:

AN:

83592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53084

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.0000262

AC:

AN:

1106334

Other (OTH)

AF:

0.00

AC:

AN:

59798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000773

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.057

Eigen

Benign

-0.12

Eigen_PC

Benign

0.018

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.81

M_CAP

Benign

0.0061

MetaRNN

Benign

0.092

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PhyloP100

0.90

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.60

REVEL

Benign

0.10

Sift

Benign

0.28

Sift4G

Benign

1.0

Polyphen

0.42

Vest4

0.36

MutPred

0.063

Loss of helix (P = 0.1299)

MVP

0.35

MPC

0.028

ClinPred

0.17

GERP RS

4.5

Varity_R

0.042

gMVP

0.091

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over