3-56557250-T-TGGGGTAAGCA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The NM_001141947.3(CCDC66):c.11+7_11+16dup variant causes a stop gained, frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 1,546,866 control chromosomes in the GnomAD database, including 517,371 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.76 (44725 hom., cov: 0)
  • Exomes 𝑓: 0.82 (472646 hom.)
• Consequence: CCDC66 NM_001141947.3 stop_gained, frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.359

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• PM4: Stoplost variant in NM_001141947.3 Downstream stopcodon found after 29 codons.
• BP6: Variant 3-56557250-T-TGGGGTAAGCA is Benign according to our data. Variant chr3-56557250-T-TGGGGTAAGCA is described in ClinVar as [Benign]. Clinvar id is 402505.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC66	NM_001141947.3	c.11+7_11+16dup		stop_gained, frameshift_variant	1/18	ENST00000394672.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC66	ENST00000394672.8	c.11+7_11+16dup		stop_gained, frameshift_variant	1/18	1	NM_001141947.3	A2

Frequencies

GnomAD3 genomes AF: 0.763 AC: 114724 AN: 150364 Hom.: 44711 Cov.: 0

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.755

GnomAD4 exome AF: 0.818 AC: 1142155 AN: 1396384 Hom.: 472646 Cov.: 66 AF XY: 0.812 AC XY: 558958 AN XY: 688646

Gnomad4 AFR exome AF: 0.610

Gnomad4 AMR exome AF: 0.760

Gnomad4 ASJ exome AF: 0.821

Gnomad4 EAS exome AF: 0.572

Gnomad4 SAS exome AF: 0.566

Gnomad4 FIN exome AF: 0.838

Gnomad4 NFE exome AF: 0.854

Gnomad4 OTH exome AF: 0.789

GnomAD4 genome AF: 0.763 AC: 114785 AN: 150482 Hom.: 44725 Cov.: 0 AF XY: 0.758 AC XY: 55644 AN XY: 73378

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.837

Gnomad4 NFE AF: 0.854

Gnomad4 OTH AF: 0.752

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 1498/2178=68.77% -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs60235683; hg19: chr3-56591278;