Variant 11-101944399-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020802.4(CEP126):c.383G>A(p.Arg128Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000117 in 1,456,680 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (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: 3.67

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP126	NM_020802.4 link	c.383G>A	p.Arg128Gln	missense_variant	3/11	ENST00000263468.13	NP_065853.3	Q9P2H0
CEP126	NM_001363543.2 link	c.-897G>A		5_prime_UTR_variant	3/12		NP_001350472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CEP126	ENST00000263468.13 link	c.383G>A	p.Arg128Gln	missense_variant	3/11	1	NM_020802.4	ENSP00000263468.8	Q9P2H0
CEP126	ENST00000532529.1 link	n.23G>A		non_coding_transcript_exon_variant	1/10	5		ENSP00000433643.1	H0YDI0
CEP126	ENST00000670091.1 link	n.383G>A		non_coding_transcript_exon_variant	3/12			ENSP00000499679.1	A0A590UK33
CEP126	ENST00000670318.1 link	n.383G>A		non_coding_transcript_exon_variant	3/12			ENSP00000499404.1	A0A590UJH0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000244

AC:

AN:

245662

Hom.:

AF XY:

0.0000377

AC XY:

AN XY:

132784

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000268

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1456680

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

724436

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000760

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000547

EpiControl

AF:

0.000179

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

Feb 28, 2023

The c.383G>A (p.R128Q) 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 383, causing the arginine (R) at amino acid position 128 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

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Pathogenic

1.0

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.91

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.55

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.16

Sift

Uncertain

0.026

Sift4G

Uncertain

0.018

Vest4

0.58

MutPred

0.21

Loss of MoRF binding (P = 0.0766);

MVP

0.55

MPC

0.57

ClinPred

0.96

GERP RS

6.0

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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