17-65641049-T-A

Variant names:

• chr17-65641049-T-A
• rs898803547
• NM_001199165.4:c.2714A>T

Variant summary

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

The NM_001199165.4(CEP112):​c.2714A>T​(p.Gln905Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,160 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CEP112 NM_001199165.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85

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]

ENSG00000266076 (HGNC:):

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
CEP112	NM_001199165.4	c.2714A>T	p.Gln905Leu	missense_variant	Exon 25 of 27	ENST00000535342.7	NP_001186094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP112	ENST00000535342.7	c.2714A>T	p.Gln905Leu	missense_variant	Exon 25 of 27	2	NM_001199165.4	ENSP00000442784.2
ENSG00000266076	ENST00000577662.1	n.-17A>T		upstream_gene_variant		2		ENSP00000462418.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447160 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 721068

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: 0.00

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2714A>T (p.Q905L) alteration is located in exon 25 (coding exon 24) of the CEP112 gene. This alteration results from a A to T substitution at nucleotide position 2714, causing the glutamine (Q) at amino acid position 905 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	0.25
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T;T;.;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.81	.;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.6	L;L;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.5	D;D;D;N
REVEL	Benign	0.19
Sift	Benign	0.35	T;T;T;T
Sift4G	Benign	0.43	T;T;D;T
Polyphen		1.0	D;D;D;D
Vest4		0.59
MutPred		0.32		Gain of catalytic residue at Q905 (P = 0.0143);Gain of catalytic residue at Q905 (P = 0.0143);.;.;
MVP		0.39
MPC		0.44
ClinPred		0.89	D
GERP RS		6.2
Varity_R		0.17
gMVP		0.32

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: rs898803547; hg19: chr17-63637167;