Genetic Variant NM_020802.4:c.266G>A (chr11-101944282-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_020802.4(CEP126):c.266G>A(p.Arg89Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,592,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CEP126
NM_020802.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.631

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:

Genome browser will be placed here

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=0.11897352).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP126	NM_020802.4 link	c.266G>A	p.Arg89Gln	missense_variant	Exon 3 of 11	ENST00000263468.13	NP_065853.3	Q9P2H0
CEP126	NM_001363543.2 link	c.-1014G>A		5_prime_UTR_variant	Exon 3 of 12		NP_001350472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CEP126	ENST00000263468.13 link	c.266G>A	p.Arg89Gln	missense_variant	Exon 3 of 11	1	NM_020802.4	ENSP00000263468.8	Q9P2H0
CEP126	ENST00000670091.1 link	n.266G>A		non_coding_transcript_exon_variant	Exon 3 of 12			ENSP00000499679.1	A0A590UK33
CEP126	ENST00000670318.1 link	n.266G>A		non_coding_transcript_exon_variant	Exon 3 of 12			ENSP00000499404.1	A0A590UJH0
CEP126	ENST00000532529.1 link	n.-95G>A		upstream_gene_variant		5		ENSP00000433643.1	H0YDI0

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151854

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000301

AC:

AN:

232886

Hom.:

AF XY:

0.0000238

AC XY:

AN XY:

126076

show subpopulations

Gnomad AFR exome

AF:

0.000262

Gnomad AMR exome

AF:

0.0000338

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000379

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000924

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1440494

Hom.:

Cov.:

AF XY:

0.0000168

AC XY:

AN XY:

715990

show subpopulations

Gnomad4 AFR exome

AF:

0.0000627

Gnomad4 AMR exome

AF:

0.0000250

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000109

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151854

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74176

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000162

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.266G>A (p.R89Q) alteration is located in exon 3 (coding exon 3) of the CEP126 gene. This alteration results from a G to A substitution at nucleotide position 266, causing the arginine (R) at amino acid position 89 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

Benign

0.076

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Benign

0.65

M_CAP

Benign

0.0086

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.2

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.13

Sift

Benign

0.032

Sift4G

Uncertain

0.025

Vest4

0.20

MutPred

0.14

Gain of ubiquitination at K90 (P = 0.039);

MVP

0.37

MPC

0.22

ClinPred

0.17

GERP RS

3.0

gMVP

0.038

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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