chr1-243142447-C-T

Variant names:

• chr1-243142447-C-T
• NM_014812.3:c.3928G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014812.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP170	NM_014812.3	MANE Select	c.3928G>A	p.Ala1310Thr	missense	Exon 15 of 20	NP_055627.2	Q5SW79-1
	CEP170	NM_001042404.2		c.3634G>A	p.Ala1212Thr	missense	Exon 14 of 19	NP_001035863.1	Q5SW79-3
	CEP170	NM_001042405.2		c.3526G>A	p.Ala1176Thr	missense	Exon 14 of 19	NP_001035864.1	Q5SW79-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP170	ENST00000366542.6	TSL:5 MANE Select	c.3928G>A	p.Ala1310Thr	missense	Exon 15 of 20	ENSP00000355500.1	Q5SW79-1
	CEP170	ENST00000366544.6	TSL:5	c.3634G>A	p.Ala1212Thr	missense	Exon 14 of 19	ENSP00000355502.1	Q5SW79-3
	CEP170	ENST00000366543.5	TSL:5	c.3526G>A	p.Ala1176Thr	missense	Exon 14 of 19	ENSP00000355501.1	Q5SW79-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.094	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	-0.014	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	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
Mutation Taster		=40/60	disease causing

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

Other links and lift over

hg19: chr1-243305749;