Variant 3-138500425-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024491.4(CEP70):c.1511G>A(p.Arg504Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000208 in 1,443,092 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: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CEP70
NM_024491.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.78

Variant links:

Genes affected

CEP70 (HGNC:29972): (centrosomal protein 70) Enables identical protein binding activity. Predicted to be involved in cilium assembly and regulation of microtubule cytoskeleton organization. Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

CEP70 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38671094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP70	NM_024491.4 linkuse as main transcript	c.1511G>A	p.Arg504Lys	missense_variant	15/18	ENST00000264982.8	NP_077817.2	Q8NHQ1-1A0A140VJG2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP70	ENST00000264982.8 linkuse as main transcript	c.1511G>A	p.Arg504Lys	missense_variant	15/18	1	NM_024491.4	ENSP00000264982.3		Q8NHQ1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000428

AC:

AN:

233444

Hom.:

AF XY:

0.00

AC XY:

AN XY:

126066

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000921

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1443092

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717270

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jul 25, 2023

The c.1511G>A (p.R504K) alteration is located in exon 15 (coding exon 13) of the CEP70 gene. This alteration results from a G to A substitution at nucleotide position 1511, causing the arginine (R) at amino acid position 504 to be replaced by a lysine (K). 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

Benign

0.14

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.067

T;.;T;.;.

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

.;T;T;T;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.39

T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.2

M;.;M;.;M

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.5

N;N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.18

T;T;T;T;T

Sift4G

Benign

0.29

T;T;T;T;T

Polyphen

0.99

D;P;D;.;D

Vest4

0.36

MutPred

0.42

Gain of ubiquitination at R504 (P = 0.0155);.;Gain of ubiquitination at R504 (P = 0.0155);.;Gain of ubiquitination at R504 (P = 0.0155);

MVP

0.56

MPC

0.30

ClinPred

0.90

GERP RS

4.9

Varity_R

0.26

gMVP

0.54

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