Variant 11-101915343-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020802.4(CEP126):c.59C>T(p.Ser20Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CEP126
NM_020802.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.91

Variant links:

Genes affected

CEP126 (HGNC:29264): (centrosomal protein 126) Involved in cilium assembly; cytoplasmic microtubule organization; and mitotic spindle organization. Located in centrosome; ciliary base; and midbody. [provided by Alliance of Genome Resources, Apr 2022]

CEP126 links:

ANGPTL5 (HGNC:19705): (angiopoietin like 5) Predicted to be active in collagen-containing extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ANGPTL5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11004946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP126	NM_020802.4 linkuse as main transcript	c.59C>T	p.Ser20Leu	missense_variant	1/11	ENST00000263468.13	NP_065853.3
ANGPTL5	NM_178127.5 linkuse as main transcript	c.-93+676G>A		intron_variant		ENST00000334289.7	NP_835228.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CEP126	ENST00000263468.13 linkuse as main transcript	c.59C>T	p.Ser20Leu	missense_variant	1/11	1	NM_020802.4	ENSP00000263468	P1
ANGPTL5	ENST00000334289.7 linkuse as main transcript	c.-93+676G>A		intron_variant		1	NM_178127.5	ENSP00000335255	P1
CEP126	ENST00000670091.1 linkuse as main transcript	c.59C>T	p.Ser20Leu	missense_variant, NMD_transcript_variant	1/12			ENSP00000499679
CEP126	ENST00000670318.1 linkuse as main transcript	c.59C>T	p.Ser20Leu	missense_variant, NMD_transcript_variant	1/12			ENSP00000499404

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250094

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135480

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:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727138

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Nov 17, 2022

The c.59C>T (p.S20L) alteration is located in exon 1 (coding exon 1) of the CEP126 gene. This alteration results from a C to T substitution at nucleotide position 59, causing the serine (S) at amino acid position 20 to be replaced by a leucine (L). 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

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.0026

M_CAP

Benign

0.011

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.5

REVEL

Benign

0.091

Sift

Benign

0.032

Sift4G

Benign

0.19

Vest4

0.21

MutPred

0.087

Loss of phosphorylation at S20 (P = 0.0268);

MVP

0.19

MPC

0.19

ClinPred

0.18

GERP RS

2.9

gMVP

0.12

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