chr12-88087719-C-CAAAAAAAAAAAAAAAAAA

Variant names:

• chr12-88087719-C-CAAAAAAAAAAAAAAAAAA
• NM_025114.4:c.4194+43_4194+60dupTTTTTTTTTTTTTTTTTT

Variant summary

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

The NM_025114.4(CEP290):​c.4194+43_4194+60dupTTTTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000041 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CEP290 NM_025114.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

Genes affected

CEP290 (HGNC:29021): (centrosomal protein 290) This gene encodes a protein with 13 putative coiled-coil domains, a region with homology to SMC chromosome segregation ATPases, six KID motifs, three tropomyosin homology domains and an ATP/GTP binding site motif A. The protein is localized to the centrosome and cilia and has sites for N-glycosylation, tyrosine sulfation, phosphorylation, N-myristoylation, and amidation. Mutations in this gene have been associated with Joubert syndrome and nephronophthisis and the presence of antibodies against this protein is associated with several forms of cancer. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP290	NM_025114.4	c.4194+43_4194+60dupTTTTTTTTTTTTTTTTTT		intron_variant	Intron 32 of 53	ENST00000552810.6	NP_079390.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP290	ENST00000552810.6	c.4194+60_4194+61insTTTTTTTTTTTTTTTTTT		intron_variant	Intron 32 of 53	1	NM_025114.4	ENSP00000448012.1

Frequencies

GnomAD3 genomes AF: 0.0000408 AC: 1 AN: 24522 Hom.: 0 Cov.: 31

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: 0.0000952

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 105132 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 52714

African (AFR) AF: 0.00 AC: 0 AN: 2470

American (AMR) AF: 0.00 AC: 0 AN: 1160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1878

East Asian (EAS) AF: 0.00 AC: 0 AN: 4720

South Asian (SAS) AF: 0.00 AC: 0 AN: 1940

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5726

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 82362

Other (OTH) AF: 0.00 AC: 0 AN: 4560

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000408 AC: 1 AN: 24522 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 12274

African (AFR) AF: 0.00 AC: 0 AN: 7206

American (AMR) AF: 0.00 AC: 0 AN: 2874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 498

East Asian (EAS) AF: 0.00 AC: 0 AN: 962

South Asian (SAS) AF: 0.00 AC: 0 AN: 728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 68

European-Non Finnish (NFE) AF: 0.0000952 AC: 1 AN: 10500

Other (OTH) AF: 0.00 AC: 0 AN: 302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-88481496;