3-134507164-A-T

Variant names:

• chr3-134507164-A-T
• NM_001353108.3:c.100A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001353108.3(CEP63):​c.100A>T​(p.Ile34Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,602 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CEP63 NM_001353108.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.38

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]

ENSG00000288700 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 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
CEP63	NM_001353108.3	c.100A>T	p.Ile34Leu	missense_variant	Exon 3 of 15	ENST00000675561.1	NP_001340037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP63	ENST00000675561.1	c.100A>T	p.Ile34Leu	missense_variant	Exon 3 of 15		NM_001353108.3	ENSP00000502085.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461602 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727114

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jan 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.100A>T (p.I34L) alteration is located in exon 4 (coding exon 2) of the CEP63 gene. This alteration results from a A to T substitution at nucleotide position 100, causing the isoleucine (I) at amino acid position 34 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.079	.;.;T;.;.;T;T;T;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;.;D;D;D;D;.;.;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.67	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.7	M;M;.;M;M;.;M;M;M
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.5	N;N;N;.;N;N;N;.;N
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D;D;D;.;D;T;D;.;D
Sift4G	Benign	0.64	T;T;T;T;T;D;T;T;T
Polyphen		1.0	D;D;.;D;D;.;D;D;D
Vest4		0.84
MutPred		0.64		Loss of methylation at K39 (P = 0.0692);Loss of methylation at K39 (P = 0.0692);Loss of methylation at K39 (P = 0.0692);Loss of methylation at K39 (P = 0.0692);Loss of methylation at K39 (P = 0.0692);Loss of methylation at K39 (P = 0.0692);Loss of methylation at K39 (P = 0.0692);Loss of methylation at K39 (P = 0.0692);Loss of methylation at K39 (P = 0.0692);
MVP		0.52
MPC		0.22
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.55
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: chr3-134226006;