Variant chr3-56621593-A-AAGAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The NM_001141947.3(CCDC66):c.2825_2828dup(p.Ser943ArgfsTer18) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,599,706 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0034 ( 9 hom. )

Consequence

CCDC66
NM_001141947.3 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.15

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM4

Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 1001 codons.

BP6

Variant 3-56621593-A-AAGAG is Benign according to our data. Variant chr3-56621593-A-AAGAG is described in ClinVar as [Likely_benign]. Clinvar id is 774299.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC66	NM_001141947.3 linkuse as main transcript	c.2825_2828dup	p.Ser943ArgfsTer18	frameshift_variant	18/18	ENST00000394672.8
TASOR	NM_001365635.2 linkuse as main transcript	c.1443_1444insCTCT		3_prime_UTR_variant	24/24	ENST00000683822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC66	ENST00000394672.8 linkuse as main transcript	c.2825_2828dup	p.Ser943ArgfsTer18	frameshift_variant	18/18	1	NM_001141947.3	A2	A2RUB6-1
TASOR	ENST00000683822.1 linkuse as main transcript	c.1443_1444insCTCT		3_prime_UTR_variant	24/24		NM_001365635.2	A2	Q9UK61-1

Frequencies

GnomAD3 genomes

AF:

0.00231

AC:

352

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000868

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00425

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00233

AC:

564

AN:

241740

Hom.:

AF XY:

0.00238

AC XY:

311

AN XY:

130752

show subpopulations

Gnomad AFR exome

AF:

0.000561

Gnomad AMR exome

AF:

0.000350

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000216

Gnomad FIN exome

AF:

0.00209

Gnomad NFE exome

AF:

0.00435

Gnomad OTH exome

AF:

0.00136

GnomAD4 exome

AF:

0.00342

AC:

4956

AN:

1447410

Hom.:

Cov.:

AF XY:

0.00342

AC XY:

2462

AN XY:

719994

show subpopulations

Gnomad4 AFR exome

AF:

0.000273

Gnomad4 AMR exome

AF:

0.000477

Gnomad4 ASJ exome

AF:

0.0000388

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.000240

Gnomad4 FIN exome

AF:

0.00143

Gnomad4 NFE exome

AF:

0.00422

Gnomad4 OTH exome

AF:

0.00270

GnomAD4 genome

AF:

0.00231

AC:

352

AN:

152296

Hom.:

Cov.:

AF XY:

0.00205

AC XY:

153

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00425

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.00223

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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