chr15-48781257-T-G

Variant names:

• chr15-48781257-T-G
• rs587783416
• NM_001194998.2:c.1516A>C

Variant summary

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

The NM_001194998.2(CEP152):​c.1516A>C​(p.Thr506Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,186 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: 0.0000021 (0 hom.)
• Consequence: CEP152 NM_001194998.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 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.1516A>C	p.Thr506Pro	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.1516A>C	p.Thr506Pro	missense_variant	Exon 12 of 27	1	NM_001194998.2	ENSP00000370337.2
CEP152	ENST00000399334.7	c.1516A>C	p.Thr506Pro	missense_variant	Exon 12 of 26	1		ENSP00000382271.3
CEP152	ENST00000325747.9	c.1237A>C	p.Thr413Pro	missense_variant	Exon 11 of 25	1		ENSP00000321000.5
CEP152	ENST00000560322.5	n.1516A>C		non_coding_transcript_exon_variant	Exon 12 of 13	1		ENSP00000453440.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249320 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135284

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: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461186 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 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: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

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	0.18
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T;.;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.2	M;M;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.026	D;D;T
Polyphen		0.93	P;.;P
Vest4		0.59
MutPred		0.23		Gain of disorder (P = 0.0505);Gain of disorder (P = 0.0505);.;
MVP		0.88
MPC		0.29
ClinPred		0.68	D
GERP RS		1.9
Varity_R		0.44
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;