CEP63 p.Met94Ile

Variant names:

• chr3-134531904-G-T
• NM_001353108.3:c.282G>T
• CEP63 p.Met94Ile

Your query was ambiguous. Multiple possible variants found:

• chr3-134531904-G-T
• chr3-134531904-G-C
• chr3-134531904-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001353108.3(CEP63):​c.282G>T​(p.Met94Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CEP63 NM_001353108.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 0 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07493794).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP63	NM_001353108.3	MANE Select	c.282G>T	p.Met94Ile	missense	Exon 4 of 15	NP_001340037.1	Q96MT8-1
	CEP63	NM_001353126.2		c.-100G>T		5_prime_UTR_premature_start_codon_gain	Exon 5 of 13	NP_001340055.1
	CEP63	NM_025180.5		c.282G>T	p.Met94Ile	missense	Exon 5 of 16	NP_079456.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP63	ENST00000675561.1	MANE Select	c.282G>T	p.Met94Ile	missense	Exon 4 of 15	ENSP00000502085.1	Q96MT8-1
	CEP63	ENST00000383229.8	TSL:1	c.282G>T	p.Met94Ile	missense	Exon 4 of 13	ENSP00000372716.3	Q96MT8-2
	CEP63	ENST00000332047.10	TSL:1	c.282G>T	p.Met94Ile	missense	Exon 4 of 12	ENSP00000328382.5	Q96MT8-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.96
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.065
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.044
Sift	Benign	0.47	T
Sift4G	Benign	0.30	T
Varity_R		0.038
gMVP		0.033
Mutation Taster		=99/1	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-134250746;