1-243142447-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP2 PP3

The NM_014812.3(CEP170):c.3928G>A(p.Ala1310Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP170 NM_014812.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90

Genes affected

CEP170 (HGNC:28920): (centrosomal protein 170) The product of this gene is a component of the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. During interphase, the encoded protein localizes to the sub-distal appendages of mature centrioles, which are microtubule-based structures thought to help organize centrosomes. During mitosis, the protein associates with spindle microtubules near the centrosomes. The protein interacts with and is phosphorylated by polo-like kinase 1, and functions in maintaining microtubule organization and cell morphology. The human genome contains a putative transcribed pseudogene. Several alternatively spliced transcript variants of this gene have been found, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, CEP170
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP170	NM_014812.3	c.3928G>A	p.Ala1310Thr	missense_variant	15/20	ENST00000366542.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP170	ENST00000366542.6	c.3928G>A	p.Ala1310Thr	missense_variant	15/20	5	NM_014812.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Dec 14, 2023

The c.3928G>A (p.A1310T) alteration is located in exon 15 (coding exon 14) of the CEP170 gene. This alteration results from a G to A substitution at nucleotide position 3928, causing the alanine (A) at amino acid position 1310 to be replaced by a threonine (T). 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	0.99
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
Cadd	Pathogenic	30
Dann	Pathogenic	1.0
DEOGEN2	Uncertain	0.53	D;.;.;.;T;.;T;T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Uncertain	0.094	D
MetaRNN	Pathogenic	0.80	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.014	T
MutationAssessor	Pathogenic	3.1	M;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.6	D;D;D;D;D;D;D;D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0020	D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;.;.
Polyphen		1.0	D;D;D;.;.;.;.;.
Vest4		0.83
MutPred		0.47		Loss of stability (P = 0.0472);.;.;.;.;.;.;.;
MVP		0.90
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.70
gMVP		0.73

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: chr1-243305749;