15-48742056-C-T

Position:

• chr15-48742056-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001194998.2(CEP152):​c.3880G>A​(p.Glu1294Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP152 NM_001194998.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.78

Genes affected

CEP152 (HGNC:29298): (centrosomal protein 152) This gene encodes a protein that is thought to be involved with centrosome function. Mutations in this gene have been associated with primary microcephaly (MCPH4). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

CEP152 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40385514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.3880G>A	p.Glu1294Lys	missense_variant	25/27	ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7	c.3880G>A	p.Glu1294Lys	missense_variant	25/27	1	NM_001194998.2	ENSP00000370337.2
CEP152	ENST00000399334.7	c.3712G>A	p.Glu1238Lys	missense_variant	24/26	1		ENSP00000382271.3
CEP152	ENST00000325747.9	c.3601G>A	p.Glu1201Lys	missense_variant	24/25	1		ENSP00000321000.5
CEP152	ENST00000561245.1	n.-42G>A		upstream_gene_variant		2		ENSP00000453591.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Microcephaly 9, primary, autosomal recessive Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 08, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.028	T;.;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.5	M;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.26
Sift	Uncertain	0.0080	D;D;T
Sift4G	Uncertain	0.019	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.53
MVP		0.79
MPC		0.39
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.52
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs12441978; hg19: chr15-49034253;