1-243136186-T-G

Variant names:

• chr1-243136186-T-G
• rs768800587
• NM_014812.3:c.4276A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014812.3(CEP170):​c.4276A>C​(p.Lys1426Gln) 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. 16/22 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. K1426E) 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: 2.02
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04169473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP170	NM_014812.3	c.4276A>C	p.Lys1426Gln	missense_variant	Exon 17 of 20	ENST00000366542.6	NP_055627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP170	ENST00000366542.6	c.4276A>C	p.Lys1426Gln	missense_variant	Exon 17 of 20	5	NM_014812.3	ENSP00000355500.1
CEP170	ENST00000366544.6	c.3982A>C	p.Lys1328Gln	missense_variant	Exon 16 of 19	5		ENSP00000355502.1
CEP170	ENST00000366543.5	c.3904A>C	p.Lys1302Gln	missense_variant	Exon 16 of 19	5		ENSP00000355501.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Benign	0.90
DEOGEN2	Benign	0.011	T;.;.;.;T;.;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.88	.;.;.;D;D;D;D
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.042	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.8	N;.;.;.;.;.;.
PhyloP100		2.0
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.80	N;N;N;N;N;N;N
REVEL	Benign	0.039
Sift	Benign	0.37	T;T;T;T;T;T;T
Sift4G	Benign	0.56	T;T;T;T;T;T;.
Polyphen		0.072	B;B;B;.;.;.;.
Vest4		0.29
MutPred		0.25		Loss of MoRF binding (P = 0.0451);.;.;.;.;.;.;
MVP		0.24
ClinPred		0.27	T
GERP RS		3.2
Varity_R		0.058
gMVP		0.082
Mutation Taster		=95/5	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: rs768800587; hg19: chr1-243299488;