NM_014812.3:c.4382G>T

Variant names:

• chr1-243129391-C-A
• rs1480474283
• NM_014812.3:c.4382G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014812.3(CEP170):​c.4382G>T​(p.Ser1461Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1461N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP170 NM_014812.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.61
• 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]

ENSG00000227230 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.4382G>T	p.Ser1461Ile	missense	Exon 18 of 20	NP_055627.2	Q5SW79-1
	CEP170	NM_001042404.2		c.4088G>T	p.Ser1363Ile	missense	Exon 17 of 19	NP_001035863.1	Q5SW79-3
	CEP170	NM_001042405.2		c.4010G>T	p.Ser1337Ile	missense	Exon 17 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.4382G>T	p.Ser1461Ile	missense	Exon 18 of 20	ENSP00000355500.1	Q5SW79-1
	CEP170	ENST00000366544.6	TSL:5	c.4088G>T	p.Ser1363Ile	missense	Exon 17 of 19	ENSP00000355502.1	Q5SW79-3
	CEP170	ENST00000366543.5	TSL:5	c.4010G>T	p.Ser1337Ile	missense	Exon 17 of 19	ENSP00000355501.1	Q5SW79-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.30		Loss of disorder (P = 0.0064)
MVP		0.74
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.70
gMVP		0.38
Mutation Taster		=55/45	polymorphism

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

Other links and lift over

dbSNP: rs1480474283; hg19: chr1-243292693;