17-65689178-C-A

Position:

• chr17-65689178-C-A

Variant summary

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

The NM_001199165.4(CEP112):​c.2648G>T​(p.Arg883Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP112 NM_001199165.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.55

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]

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/exons	MANE	UniProt
CEP112	NM_001199165.4	c.2648G>T	p.Arg883Leu	missense_variant	24/27	ENST00000535342.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP112	ENST00000535342.7	c.2648G>T	p.Arg883Leu	missense_variant	24/27	2	NM_001199165.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2023

The c.2648G>T (p.R883L) alteration is located in exon 24 (coding exon 23) of the CEP112 gene. This alteration results from a G to T substitution at nucleotide position 2648, causing the arginine (R) at amino acid position 883 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;T;.;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	.;D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.50	D;D;D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.9	L;L;.;.
MutationTaster	Benign	0.62	D;D;D;D;N
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Benign	0.13
Sift	Uncertain	0.012	D;D;D;D
Sift4G	Benign	0.76	T;T;D;T
Polyphen		0.99	D;D;D;D
Vest4		0.66
MutPred		0.22		Loss of MoRF binding (P = 0.028);Loss of MoRF binding (P = 0.028);.;.;
MVP		0.43
MPC		0.49
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.26
gMVP		0.42

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: chr17-63685296;