rs11225089

Positions:

• chr11-101961859-C-A
• chr11-101961859-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.056 (470 hom., cov: 32)
  • Exomes 𝑓: 0.057 (3943 hom.)
• Consequence: CEP126 NM_020802.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04

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]

ACMG classification

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	c.824C>A	p.Ser275Tyr	missense_variant	6/11	ENST00000263468.13	NP_065853.3
CEP126	NM_001363543.2	c.227C>A	p.Ser76Tyr	missense_variant	7/12		NP_001350472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP126	ENST00000263468.13	c.824C>A	p.Ser275Tyr	missense_variant	6/11	1	NM_020802.4	ENSP00000263468.8

Frequencies

GnomAD3 genomes AF: 0.0561 AC: 8527 AN: 151984 Hom.: 473 Cov.: 32

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

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.: 31 AF XY: 0.0583 AC XY: 42179 AN XY: 723798

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.: 32 AF XY: 0.0633 AC XY: 4705 AN XY: 74348

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	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	0.015
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.40	N
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.077
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Vest4		0.086
MPC		0.54
ClinPred		0.025	T
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

Other links and lift over

dbSNP: rs11225089; hg19: chr11-101832590; COSMIC: COSV54822446;