17-65689142-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001199165.4(CEP112):c.2684A>C(p.Glu895Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,458,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CEP112 NM_001199165.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.04

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24153581).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP112	NM_001199165.4	c.2684A>C	p.Glu895Ala	missense_variant	24/27	ENST00000535342.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP112	ENST00000535342.7	c.2684A>C	p.Glu895Ala	missense_variant	24/27	2	NM_001199165.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1458480 Hom.: 0 Cov.: 29 AF XY: 0.00000413 AC XY: 3 AN XY: 725822

Gnomad4 AFR exome AF: 0.000120

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

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

Jun 23, 2021

The c.2684A>C (p.E895A) alteration is located in exon 24 (coding exon 23) of the CEP112 gene. This alteration results from a A to C substitution at nucleotide position 2684, causing the glutamic acid (E) at amino acid position 895 to be replaced by an alanine (A). 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	0.12
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.043	T;T;.;.
Eigen	Benign	-0.019
Eigen_PC	Benign	0.076
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.3	L;L;.;.
MutationTaster	Benign	0.80	D;D;N;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.8	N;N;D;N
REVEL	Benign	0.21
Sift	Benign	0.17	T;T;T;T
Sift4G	Benign	0.18	T;T;T;T
Polyphen		0.70	P;P;P;P
Vest4		0.53
MutPred		0.083		Loss of ubiquitination at K892 (P = 0.0345);Loss of ubiquitination at K892 (P = 0.0345);.;.;
MVP		0.31
MPC		0.12
ClinPred		0.91	D
GERP RS		4.5
Varity_R		0.11
gMVP		0.34

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

LitVar

Other links and lift over

dbSNP: rs950016636; hg19: chr17-63685260;