11-101944282-G-T

Variant names:

• chr11-101944282-G-T
• rs145886481
• NM_020802.4:c.266G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020802.4(CEP126):​c.266G>T​(p.Arg89Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R89Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CEP126 NM_020802.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1881881).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020802.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP126	NM_020802.4	MANE Select	c.266G>T	p.Arg89Leu	missense	Exon 3 of 11	NP_065853.3	Q9P2H0
	CEP126	NM_001363543.2		c.-1014G>T		5_prime_UTR	Exon 3 of 12	NP_001350472.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP126	ENST00000263468.13	TSL:1 MANE Select	c.266G>T	p.Arg89Leu	missense	Exon 3 of 11	ENSP00000263468.8	Q9P2H0
	CEP126	ENST00000931861.1		c.266G>T	p.Arg89Leu	missense	Exon 3 of 11	ENSP00000601920.1
	CEP126	ENST00000670091.1		n.266G>T		non_coding_transcript_exon	Exon 3 of 12	ENSP00000499679.1	A0A590UK33

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440494 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 715990

African (AFR) AF: 0.00 AC: 0 AN: 31920

American (AMR) AF: 0.00 AC: 0 AN: 40042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25680

East Asian (EAS) AF: 0.00 AC: 0 AN: 38584

South Asian (SAS) AF: 0.00 AC: 0 AN: 80888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5618

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105096

Other (OTH) AF: 0.0000168 AC: 1 AN: 59436

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	1.0
Eigen	Benign	0.060
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.73	D
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.63
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.13
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.011	D
Vest4		0.40
MutPred		0.17		Gain of ubiquitination at K90 (P = 0.0399)
MVP		0.29
MPC		0.53
ClinPred		0.78	D
GERP RS		3.0
gMVP		0.068
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs145886481; hg19: chr11-101815013;