3-134549149-C-G

Variant names:

• chr3-134549149-C-G
• NM_001353108.3:c.1155C>G
• CEP63 p.Asn385Lys

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.1155C>G​(p.Asn385Lys) 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. 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 Benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N385T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP63 NM_001353108.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• 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=0.13736856).

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.1155C>G	p.Asn385Lys	missense	Exon 10 of 15	NP_001340037.1	Q96MT8-1
	CEP63	NM_025180.5		c.1155C>G	p.Asn385Lys	missense	Exon 11 of 16	NP_079456.2
	CEP63	NM_001353109.1		c.1017C>G	p.Asn339Lys	missense	Exon 9 of 14	NP_001340038.1	A0A804HIX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP63	ENST00000675561.1	MANE Select	c.1155C>G	p.Asn385Lys	missense	Exon 10 of 15	ENSP00000502085.1	Q96MT8-1
	CEP63	ENST00000383229.8	TSL:1	c.1155C>G	p.Asn385Lys	missense	Exon 10 of 13	ENSP00000372716.3	Q96MT8-2
	CEP63	ENST00000332047.10	TSL:1	c.1017C>G	p.Asn339Lys	missense	Exon 9 of 12	ENSP00000328382.5	Q96MT8-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T
Eigen	Benign	0.049
Eigen_PC	Benign	0.087
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.3
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.049
Sift	Benign	0.47	T
Sift4G	Benign	1.0	T
Varity_R		0.068
gMVP		0.18
Mutation Taster		=97/3	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: chr3-134267991;