NM_014812.3:c.4582C>G

Variant names:

• chr1-243126622-G-C
• rs779506534
• NM_014812.3:c.4582C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014812.3(CEP170):​c.4582C>G​(p.His1528Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 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. H1528Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CEP170 NM_014812.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029604614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP170	NM_014812.3	c.4582C>G	p.His1528Asp	missense_variant	Exon 20 of 20	ENST00000366542.6	NP_055627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP170	ENST00000366542.6	c.4582C>G	p.His1528Asp	missense_variant	Exon 20 of 20	5	NM_014812.3	ENSP00000355500.1
CEP170	ENST00000366544.5	c.4288C>G	p.His1430Asp	missense_variant	Exon 19 of 19	5		ENSP00000355502.1
CEP170	ENST00000366543.5	c.4210C>G	p.His1404Asp	missense_variant	Exon 19 of 19	5		ENSP00000355501.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.60
DEOGEN2	Benign	0.0090	T;.;.;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.82	.;.;.;T;T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.030	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;.;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.27	N;N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.39	T;T;T;T;T
Sift4G	Benign	0.64	T;T;T;T;T
Polyphen		0.0	B;B;B;.;.
Vest4		0.11
MutPred		0.061		Gain of relative solvent accessibility (P = 0.09);.;.;.;.;
MVP		0.23
ClinPred		0.015	T
GERP RS		-3.5
Varity_R		0.024
gMVP		0.23

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: rs779506534; hg19: chr1-243289924;