chr11-101958364-C-A

Position:

• chr11-101958364-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020802.4(CEP126):​c.703C>A​(p.Gln235Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP126 NM_020802.4 missense, splice_region
• Scores: Splicing: ADA: 0.8730
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96

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 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=0.26086795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP126	NM_020802.4	c.703C>A	p.Gln235Lys	missense_variant, splice_region_variant	5/11	ENST00000263468.13	NP_065853.3
CEP126	NM_001363543.2	c.106C>A	p.Gln36Lys	missense_variant, splice_region_variant	6/12		NP_001350472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP126	ENST00000263468.13	c.703C>A	p.Gln235Lys	missense_variant, splice_region_variant	5/11	1	NM_020802.4	ENSP00000263468.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2023

The c.703C>A (p.Q235K) alteration is located in exon 5 (coding exon 5) of the CEP126 gene. This alteration results from a C to A substitution at nucleotide position 703, causing the glutamine (Q) at amino acid position 235 to be replaced by a lysine (K). 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	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.2	T
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.11
Sift	Uncertain	0.026	D
Sift4G	Benign	0.067	T
Vest4		0.32
MutPred		0.17		Gain of ubiquitination at Q235 (P = 0.0155);
MVP		0.46
MPC		0.54
ClinPred		0.96	D
GERP RS		5.6
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.87
dbscSNV1_RF	Benign	0.70
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-101829095;