rs587783416

chr15-48781257-T-Cchr15-48781257-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001194998.2(CEP152):c.1516A>G(p.Thr506Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CEP152 NM_001194998.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.328

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12958664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP152	NM_001194998.2	c.1516A>G	p.Thr506Ala	missense_variant	12/27	ENST00000380950.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP152	ENST00000380950.7	c.1516A>G	p.Thr506Ala	missense_variant	12/27	1	NM_001194998.2	A2
CEP152	ENST00000399334.7	c.1516A>G	p.Thr506Ala	missense_variant	12/26	1		P2
CEP152	ENST00000325747.9	c.1237A>G	p.Thr413Ala	missense_variant	11/25	1		A2
CEP152	ENST00000560322.5	c.1516A>G	p.Thr506Ala	missense_variant	12/13	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461186 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726940

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000506

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	14
Dann	Benign	0.80
DEOGEN2	Benign	0.0048	T;.;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.54	T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.6	L;L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.76	N;N;N
REVEL	Benign	0.095
Sift	Benign	0.095	T;T;T
Sift4G	Benign	0.25	T;T;T
Polyphen		0.010	B;.;B
Vest4		0.34
MutPred		0.18		Loss of catalytic residue at T506 (P = 0.1395);Loss of catalytic residue at T506 (P = 0.1395);.;
MVP		0.70
MPC		0.064
ClinPred		0.090	T
GERP RS		1.9
Varity_R		0.049
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs587783416; hg19: chr15-49073454;