3-56557250-TGGGGTAAGCA-TGGGGTAAGCAGGGGTAAGCAGGGGTAAGCA

Position:

• chr3-56557250-TGGGGTAAGCA-TGGGGTAAGCAGGGGTAAGCAGGGGTAAGCA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001353153.1(CCDC66):​c.-92+6_-92+7insAGGGGTAAGCAGGGGTAAGC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000249 in 1,547,076 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00072 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00020 (2 hom.)
• Consequence: CCDC66 NM_001353153.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• 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]

CCDC66 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC66	NM_001141947.3	c.11+16_11+17insAGGGGTAAGCAGGGGTAAGC		intron_variant		ENST00000394672.8	NP_001135419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC66	ENST00000394672.8	c.11+16_11+17insAGGGGTAAGCAGGGGTAAGC		intron_variant		1	NM_001141947.3	ENSP00000378167.3

Frequencies

GnomAD3 genomes AF: 0.000725 AC: 109 AN: 150444 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00146

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000200

Gnomad SAS AF: 0.00106

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000739

Gnomad OTH AF: 0.00194

GnomAD4 exome AF: 0.000198 AC: 276 AN: 1396514 Hom.: 2 Cov.: 66 AF XY: 0.000184 AC XY: 127 AN XY: 688724

Gnomad4 AFR exome AF: 0.00190

Gnomad4 AMR exome AF: 0.000196

Gnomad4 ASJ exome AF: 0.000994

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.000379

Gnomad4 FIN exome AF: 0.0000205

Gnomad4 NFE exome AF: 0.000119

Gnomad4 OTH exome AF: 0.000397

GnomAD4 genome AF: 0.000724 AC: 109 AN: 150562 Hom.: 0 Cov.: 0 AF XY: 0.000763 AC XY: 56 AN XY: 73418

Gnomad4 AFR AF: 0.00161

Gnomad4 AMR AF: 0.00145

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000200

Gnomad4 SAS AF: 0.00106

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000739

Gnomad4 OTH AF: 0.00192

ClinVar

Not reported in ClinVar

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;