Variant 3-134507164-A-T details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.38

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
CEP63	NM_001353108.3 linkuse as main transcript	c.100A>T	p.Ile34Leu	missense_variant	3/15	ENST00000675561.1	NP_001340037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP63	ENST00000675561.1 linkuse as main transcript	c.100A>T	p.Ile34Leu	missense_variant	3/15		NM_001353108.3	ENSP00000502085	A1	Q96MT8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461602

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727114

show subpopulations

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

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

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

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

LIST_S2

Uncertain

0.94

D;.;D;D;D;D;.;.;D

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.67

D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.7

M;M;.;M;M;.;M;M;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.76

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over