Variant rs11225089 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020802.4(CEP126):c.824C>A(p.Ser275Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0566 in 1,606,672 control chromosomes in the GnomAD database, including 4,413 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.056 ( 470 hom., cov: 32)

Exomes 𝑓: 0.057 ( 3943 hom. )

Consequence

CEP126
NM_020802.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.04

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050222874).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP126	NM_020802.4 linkuse as main transcript	c.824C>A	p.Ser275Tyr	missense_variant	6/11	ENST00000263468.13	NP_065853.3
CEP126	NM_001363543.2 linkuse as main transcript	c.227C>A	p.Ser76Tyr	missense_variant	7/12		NP_001350472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CEP126	ENST00000263468.13 linkuse as main transcript	c.824C>A	p.Ser275Tyr	missense_variant	6/11	1	NM_020802.4	ENSP00000263468	P1
CEP126	ENST00000532529.1 linkuse as main transcript	c.*320C>A		3_prime_UTR_variant, NMD_transcript_variant	5/10	5		ENSP00000433643
CEP126	ENST00000670091.1 linkuse as main transcript	c.*867C>A		3_prime_UTR_variant, NMD_transcript_variant	7/12			ENSP00000499679
CEP126	ENST00000670318.1 linkuse as main transcript	c.*336C>A		3_prime_UTR_variant, NMD_transcript_variant	7/12			ENSP00000499404

Frequencies

GnomAD3 genomes

AF:

0.0561

AC:

8527

AN:

151984

Hom.:

473

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0211

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0884

Gnomad ASJ

AF:

0.0205

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.166

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0410

Gnomad OTH

AF:

0.0492

GnomAD3 exomes

AF:

0.0834

AC:

20764

AN:

248924

Hom.:

1587

AF XY:

0.0823

AC XY:

11076

AN XY:

134542

show subpopulations

Gnomad AFR exome

AF:

0.0219

Gnomad AMR exome

AF:

0.131

Gnomad ASJ exome

AF:

0.0179

Gnomad EAS exome

AF:

0.281

Gnomad SAS exome

AF:

0.131

Gnomad FIN exome

AF:

0.0972

Gnomad NFE exome

AF:

0.0379

Gnomad OTH exome

AF:

0.0594

GnomAD4 exome

AF:

0.0566

AC:

82369

AN:

1454570

Hom.:

3943

Cov.:

AF XY:

0.0583

AC XY:

42179

AN XY:

723798

show subpopulations

Gnomad4 AFR exome

AF:

0.0178

Gnomad4 AMR exome

AF:

0.121

Gnomad4 ASJ exome

AF:

0.0214

Gnomad4 EAS exome

AF:

0.238

Gnomad4 SAS exome

AF:

0.137

Gnomad4 FIN exome

AF:

0.0945

Gnomad4 NFE exome

AF:

0.0414

Gnomad4 OTH exome

AF:

0.0603

GnomAD4 genome

AF:

0.0560

AC:

8520

AN:

152102

Hom.:

470

Cov.:

AF XY:

0.0633

AC XY:

4705

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0211

Gnomad4 AMR

AF:

0.0885

Gnomad4 ASJ

AF:

0.0205

Gnomad4 EAS

AF:

0.267

Gnomad4 SAS

AF:

0.165

Gnomad4 FIN

AF:

0.107

Gnomad4 NFE

AF:

0.0410

Gnomad4 OTH

AF:

0.0487

Alfa

AF:

0.0452

Hom.:

654

Bravo

AF:

0.0540

TwinsUK

AF:

0.0429

AC:

159

ALSPAC

AF:

0.0392

AC:

151

ESP6500AA

AF:

0.0254

AC:

112

ESP6500EA

AF:

0.0388

AC:

334

ExAC

AF:

0.0820

AC:

9959

Asia WGS

AF:

0.183

AC:

638

AN:

3476

EpiCase

AF:

0.0362

EpiControl

AF:

0.0360

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

0.015

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.40

MetaRNN

Benign

0.0050

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.077

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Vest4

0.086

MPC

0.54

ClinPred

0.025

GERP RS

3.9

gMVP

0.17

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over