rs267606717

Variant names:

• chr15-48793359-T-A
• NM_001194998.2:c.794A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-48793359-T-A
• chr15-48793359-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM5 PP3

The NM_001194998.2(CEP152):​c.794A>T​(p.Gln265Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. Q265P) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP152 NM_001194998.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.24

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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr15-48793359-T-G is described in Lovd as [Pathogenic].
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.794A>T	p.Gln265Leu	missense_variant	Exon 7 of 27	ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7	c.794A>T	p.Gln265Leu	missense_variant	Exon 7 of 27	1	NM_001194998.2	ENSP00000370337.2
CEP152	ENST00000399334.7	c.794A>T	p.Gln265Leu	missense_variant	Exon 7 of 26	1		ENSP00000382271.3
CEP152	ENST00000325747.9	c.515A>T	p.Gln172Leu	missense_variant	Exon 6 of 25	1		ENSP00000321000.5
CEP152	ENST00000560322.5	n.794A>T		non_coding_transcript_exon_variant	Exon 7 of 13	1		ENSP00000453440.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Uncertain	0.56	D
MutationAssessor	Uncertain	2.7	M;M;.
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-4.7	D;D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0040	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.72
MutPred		0.25		Loss of disorder (P = 0.0384);Loss of disorder (P = 0.0384);.;
MVP		0.96
MPC		0.39
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.44
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-49085556;