1-243129430-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_014812.3(CEP170):c.4343G>A(p.Arg1448Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000641 in 1,559,728 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

CEP170
NM_014812.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.38

Publications

0 publications found

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:

ENSG00000227230 (HGNC:):

ENSG00000227230 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP170	NM_014812.3 link	c.4343G>A	p.Arg1448Gln	missense_variant	Exon 18 of 20	ENST00000366542.6	NP_055627.2	Q5SW79-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CEP170	ENST00000366542.6 link	c.4343G>A	p.Arg1448Gln	missense_variant	Exon 18 of 20	5	NM_014812.3	ENSP00000355500.1	Q5SW79-1
CEP170	ENST00000366544.6 link	c.4049G>A	p.Arg1350Gln	missense_variant	Exon 17 of 19	5		ENSP00000355502.1	Q5SW79-3
CEP170	ENST00000366543.5 link	c.3971G>A	p.Arg1324Gln	missense_variant	Exon 17 of 19	5		ENSP00000355501.1	Q5SW79-2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000639

AC:

AN:

1407850

Hom.:

Cov.:

AF XY:

0.00000715

AC XY:

AN XY:

699710

show subpopulations

African (AFR)

AF:

0.0000314

AC:

AN:

31824

American (AMR)

AF:

0.00

AC:

AN:

39316

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24888

East Asian (EAS)

AF:

0.00

AC:

AN:

38856

South Asian (SAS)

AF:

0.00

AC:

AN:

77966

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51668

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5582

European-Non Finnish (NFE)

AF:

0.00000648

AC:

AN:

1079688

Other (OTH)

AF:

0.0000172

AC:

AN:

58062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151878

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74170

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000242

AC:

AN:

41384

American (AMR)

AF:

0.00

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67934

Other (OTH)

AF:

0.00

AC:

AN:

2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 24, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.4343G>A (p.R1448Q) alteration is located in exon 18 (coding exon 17) of the CEP170 gene. This alteration results from a G to A substitution at nucleotide position 4343, causing the arginine (R) at amino acid position 1448 to be replaced by a glutamine (Q). 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

0.40

BayesDel_addAF

Uncertain

0.072

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.34

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

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

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

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.46

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

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.9

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

PhyloP100

6.4

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.9

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

REVEL

Benign

0.24

Sift

Pathogenic

0.0

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

Sift4G

Uncertain

0.0080

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

Polyphen

1.0

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

Vest4

0.45

MutPred

0.29

Loss of MoRF binding (P = 0.019);.;.;.;.;.;.;

MVP

0.77

ClinPred

1.0

GERP RS

5.0

Varity_R

0.75

gMVP

0.30

Mutation Taster

=60/40

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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1-243129430-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over