chr17-65961487-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001199165.4(CEP112):c.1848A>C(p.Lys616Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,610,918 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
CEP112
NM_001199165.4 missense
NM_001199165.4 missense
Scores
8
10
Clinical Significance
Conservation
PhyloP100: 0.705
Genes affected
CEP112 (HGNC:28514): (centrosomal protein 112) This gene encodes a coiled-coil domain containing protein that belongs to the cell division control protein 42 effector protein family. In neurons, it localizes to the cytoplasm of dendrites and is also enriched in the nucleus where it interacts with the RNA polymerase III transcriptional repressor Maf1 to regulate gamma-aminobutyric acid A receptor surface expression. In addition, the protein has been identified as a component of the human centrosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]
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ACMG classification
Classification made for transcript
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP112 | NM_001199165.4 | c.1848A>C | p.Lys616Asn | missense_variant | 18/27 | ENST00000535342.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP112 | ENST00000535342.7 | c.1848A>C | p.Lys616Asn | missense_variant | 18/27 | 2 | NM_001199165.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1458706Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2AN XY: 725370
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74370
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 13, 2021 | The c.1848A>C (p.K616N) alteration is located in exon 18 (coding exon 17) of the CEP112 gene. This alteration results from a A to C substitution at nucleotide position 1848, causing the lysine (K) at amino acid position 616 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;T
Polyphen
D;D;D
Vest4
MutPred
Loss of ubiquitination at K616 (P = 0.0017);Loss of ubiquitination at K616 (P = 0.0017);.;
MVP
MPC
0.45
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at