rs60235683

Variant names:

• chr3-56557250-TGGGGTAAGCA-T
• rs60235683
• NM_001141947.3:c.11+7_11+16delAGGGGTAAGC

Your query was ambiguous. Multiple possible variants found:

• chr3-56557250-TGGGGTAAGCA-T
• chr3-56557250-TGGGGTAAGCA-TGGGGTAAGCAGGGGTAAGCA
• chr3-56557250-TGGGGTAAGCA-TGGGGTAAGCAGGGGTAAGCAGGGGTAAGCA
• chr3-56557250-TGGGGTAAGCA-TGGGGTAAGCAGGGGTAAGCAGGGGTAAGCAGGGGTAAGCA
• chr3-56557250-TGGGGTAAGCA-TGGGGTAAGCAGGGGTAAGCAGGGGTAAGCTGGGGTAAGCAGGGGTAAGCA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001141947.3(CCDC66):​c.11+7_11+16delAGGGGTAAGC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,546,964 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: CCDC66 NM_001141947.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.42
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC66	NM_001141947.3	c.11+7_11+16delAGGGGTAAGC		splice_region_variant, intron_variant	Intron 1 of 17	ENST00000394672.8	NP_001135419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC66	ENST00000394672.8	c.9_11+7delGGGGTAAGCA	p.Gly4del	splice_donor_variant, disruptive_inframe_deletion, splice_region_variant, intron_variant	Exon 1 of 18	1	NM_001141947.3	ENSP00000378167.3

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 150448 Hom.: 0 Cov.: 0

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: 0.0000963

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000129 AC: 18 AN: 1396516 Hom.: 0 AF XY: 0.0000145 AC XY: 10 AN XY: 688726

African (AFR) AF: 0.0000317 AC: 1 AN: 31554

American (AMR) AF: 0.00 AC: 0 AN: 35640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25140

East Asian (EAS) AF: 0.00 AC: 0 AN: 35704

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79180

European-Finnish (FIN) AF: 0.0000615 AC: 3 AN: 48776

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00000929 AC: 10 AN: 1076896

Other (OTH) AF: 0.0000518 AC: 3 AN: 57938

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150448 Hom.: 0 Cov.: 0 AF XY: 0.0000136 AC XY: 1 AN XY: 73292

African (AFR) AF: 0.00 AC: 0 AN: 40862

American (AMR) AF: 0.00 AC: 0 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 4998

South Asian (SAS) AF: 0.00 AC: 0 AN: 4704

European-Finnish (FIN) AF: 0.0000963 AC: 1 AN: 10386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67634

Other (OTH) AF: 0.00 AC: 0 AN: 2060

Alfa AF: 0.00 Hom.: 4713

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4

Splicing

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

Other links and lift over

dbSNP: rs60235683; hg19: chr3-56591278;