chr1-243136201-C-T

Position:

chr1-243136201-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014812.3(CEP170):c.4261G>A(p.Val1421Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 151,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000068 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CEP170
NM_014812.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.25

Variant links:

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]

CEP170 links:

CEP170 (HGNC:):

CEP170 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15979499).

BS2

High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP170	NM_014812.3 linkuse as main transcript	c.4261G>A	p.Val1421Ile	missense_variant	17/20	ENST00000366542.6	NP_055627.2	Q5SW79-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CEP170	ENST00000366542.6 linkuse as main transcript	c.4261G>A	p.Val1421Ile	missense_variant	17/20	5	NM_014812.3	ENSP00000355500.1	Q5SW79-1
CEP170	ENST00000366544.5 linkuse as main transcript	c.3967G>A	p.Val1323Ile	missense_variant	16/19	5		ENSP00000355502.1	Q5SW79-3
CEP170	ENST00000366543.5 linkuse as main transcript	c.3889G>A	p.Val1297Ile	missense_variant	16/19	5		ENSP00000355501.1	Q5SW79-2

Frequencies

GnomAD3 genomes

AF:

0.000119

AC:

AN:

151720

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000315

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000957

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000678

AC:

AN:

1385840

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

682816

show subpopulations

Gnomad4 AFR exome

AF:

0.000616

Gnomad4 AMR exome

AF:

0.000154

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000112

Gnomad4 SAS exome

AF:

0.000143

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000457

Gnomad4 OTH exome

AF:

0.0000870

GnomAD4 genome

AF:

0.000119

AC:

AN:

151838

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.000314

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000144

Hom.:

ExAC

AF:

0.000116

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.4261G>A (p.V1421I) alteration is located in exon 17 (coding exon 16) of the CEP170 gene. This alteration results from a G to A substitution at nucleotide position 4261, causing the valine (V) at amino acid position 1421 to be replaced by an isoleucine (I). 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

Uncertain

0.43

BayesDel_addAF

Uncertain

0.087

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.;.;.;T;.;T

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

.;.;.;D;D;D;D

M_CAP

Benign

0.048

MetaRNN

Benign

0.16

T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.23

MutationAssessor

Pathogenic

3.1

M;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.88

N;N;N;N;N;N;N

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;.

Polyphen

1.0

D;D;D;.;.;.;.

Vest4

0.44

MutPred

0.21

Gain of MoRF binding (P = 0.1281);.;.;.;.;.;.;

MVP

0.55

ClinPred

0.22

GERP RS

4.4

Varity_R

0.42

gMVP

0.31

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over