chr3-134545716-GC-TT

Variant names:

• chr3-134545716-GC-TT
• rs796503097
• NM_001353108.3:c.686_687delGCinsTT

Variant summary

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

The NM_001353108.3(CEP63):​c.686_687delGCinsTT​(p.Arg229Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.0000319 in 8 alleles, including 0 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as not provided (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R229C) has been classified as Uncertain significance.

• Frequency: GnomAD MNV: 𝑓 0.000032 Genomes: not found (cov: 32)
• Consequence: CEP63 NM_001353108.3 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 5.36
• Publications: 3 publications found

Genes affected

CEP63 (HGNC:25815): (centrosomal protein 63) This gene encodes a protein with six coiled-coil domains. The protein is localized to the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. Several alternatively spliced transcript variants have been found, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

CEP63 Gene-Disease associations (from GenCC):

• Seckel syndrome 6

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000288700 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353108.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP63	NM_001353108.3	MANE Select	c.686_687delGCinsTT	p.Arg229Leu	missense	N/A	NP_001340037.1
	CEP63	NM_025180.5		c.686_687delGCinsTT	p.Arg229Leu	missense	N/A	NP_079456.2
	CEP63	NM_001353109.1		c.686_687delGCinsTT	p.Arg229Leu	missense	N/A	NP_001340038.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP63	ENST00000675561.1	MANE Select	c.686_687delGCinsTT	p.Arg229Leu	missense	N/A	ENSP00000502085.1
	CEP63	ENST00000383229.8	TSL:1	c.686_687delGCinsTT	p.Arg229Leu	missense	N/A	ENSP00000372716.3
	CEP63	ENST00000332047.10	TSL:1	c.686_687delGCinsTT	p.Arg229Leu	missense	N/A	ENSP00000328382.5

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

GnomAD MNV AF: 0.0000319 AC: 8 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	Developmental dyslexia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.4
Mutation Taster		=0/100	disease causing

Splicing

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

Other links and lift over

dbSNP: rs796503097; hg19: chr3-134264558;