17-65637187-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001199165.4(CEP112):c.2801T>C(p.Val934Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000685 in 1,460,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CEP112 NM_001199165.4 missense, splice_region
• Scores: Splicing: ADA: 0.3867
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.16

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36945897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP112	NM_001199165.4	c.2801T>C	p.Val934Ala	missense_variant, splice_region_variant	26/27	ENST00000535342.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP112	ENST00000535342.7	c.2801T>C	p.Val934Ala	missense_variant, splice_region_variant	26/27	2	NM_001199165.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460888 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726828

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Dec 16, 2023

The c.2801T>C (p.V934A) alteration is located in exon 26 (coding exon 25) of the CEP112 gene. This alteration results from a T to C substitution at nucleotide position 2801, causing the valine (V) at amino acid position 934 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	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;T;.;.
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.37	T;T;T;T;T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	1.8	L;L;.;.;.
MutationTaster	Benign	0.88	D;D;D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.4	N;N;.;D;N
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D;D;.;D;D
Sift4G	Benign	0.14	T;T;T;D;T
Polyphen		1.0	D;D;.;D;D
Vest4		0.73
MutPred		0.30		Gain of disorder (P = 0.0255);Gain of disorder (P = 0.0255);.;.;.;
MVP		0.51
MPC		0.37
ClinPred		0.95	D
GERP RS		5.2
Varity_R		0.33
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.39
dbscSNV1_RF	Benign	0.36
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.24		Position offset: 1

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: chr17-63633305;