15-48781208-G-T

Variant names:

• chr15-48781208-G-T
• NM_001194998.2:c.1565C>A

Variant summary

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

The NM_001194998.2(CEP152):​c.1565C>A​(p.Ser522Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,058 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CEP152 NM_001194998.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.00

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.1565C>A	p.Ser522Tyr	missense_variant	Exon 12 of 27	ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7	c.1565C>A	p.Ser522Tyr	missense_variant	Exon 12 of 27	1	NM_001194998.2	ENSP00000370337.2
CEP152	ENST00000399334.7	c.1565C>A	p.Ser522Tyr	missense_variant	Exon 12 of 26	1		ENSP00000382271.3
CEP152	ENST00000325747.9	c.1286C>A	p.Ser429Tyr	missense_variant	Exon 11 of 25	1		ENSP00000321000.5
CEP152	ENST00000560322.5	n.1565C>A		non_coding_transcript_exon_variant	Exon 12 of 13	1		ENSP00000453440.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461058 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726878

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;.;.
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Uncertain	0.26	D
MutationAssessor	Uncertain	2.6	M;M;.
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.013	D;D;D
Sift4G	Uncertain	0.015	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.52
MutPred		0.23		Loss of disorder (P = 0.0055);Loss of disorder (P = 0.0055);.;
MVP		0.94
MPC		0.39
ClinPred		0.93	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.37
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-49073405;