chr15-48756508-G-A

Position:

• chr15-48756508-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001194998.2(CEP152):​c.2740C>T​(p.Leu914Phe) 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. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. L914V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP152 NM_001194998.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.829

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06771088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.2740C>T	p.Leu914Phe	missense_variant	20/27	ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7	c.2740C>T	p.Leu914Phe	missense_variant	20/27	1	NM_001194998.2	ENSP00000370337.2
CEP152	ENST00000399334.7	c.2740C>T	p.Leu914Phe	missense_variant	20/26	1		ENSP00000382271.3
CEP152	ENST00000325747.9	c.2461C>T	p.Leu821Phe	missense_variant	19/25	1		ENSP00000321000.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0079	T;.;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.60	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.068	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M;M;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.069
Sift	Benign	0.39	T;T;T
Sift4G	Benign	0.56	T;T;T
Polyphen		0.75	P;.;B
Vest4		0.16
MutPred		0.20		Gain of ubiquitination at K909 (P = 0.0945);Gain of ubiquitination at K909 (P = 0.0945);.;
MVP		0.54
MPC		0.34
ClinPred		0.31	T
GERP RS		0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.038
gMVP		0.056

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs16961560; hg19: chr15-49048705;