15-48738304-G-T

Variant names:

• chr15-48738304-G-T
• rs368764302
• NM_001194998.2:c.5078C>A

Variant summary

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

The NM_001194998.2(CEP152):​c.5078C>A​(p.Pro1693Gln) 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 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P1693P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CEP152 NM_001194998.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.945

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=0.25503218).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.5078C>A	p.Pro1693Gln	missense_variant	Exon 27 of 27	ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7	c.5078C>A	p.Pro1693Gln	missense_variant	Exon 27 of 27	1	NM_001194998.2	ENSP00000370337.2
CEP152	ENST00000399334.7	c.4910C>A	p.Pro1637Gln	missense_variant	Exon 26 of 26	1		ENSP00000382271.3
CEP152	ENST00000561245.1	n.142+3327C>A		intron_variant	Intron 2 of 3	2		ENSP00000453591.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000803 AC: 2 AN: 249196 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135212

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461728 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727148

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.093
Sift	Uncertain	0.025	D;D
Sift4G	Benign	0.25	T;T
Vest4		0.38
MVP		0.67
MPC		0.38
ClinPred		0.72	D
GERP RS		2.7
Varity_R		0.049
gMVP		0.039

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: rs368764302; hg19: chr15-49030501; COSMIC: COSV100359025; COSMIC: COSV100359025;