11-101961873-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020802.4(CEP126):c.838A>G(p.Thr280Ala) variant causes a missense 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CEP126 NM_020802.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.970

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035532355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP126	NM_020802.4	c.838A>G	p.Thr280Ala	missense_variant	6/11	ENST00000263468.13
CEP126	NM_001363543.2	c.241A>G	p.Thr81Ala	missense_variant	7/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP126	ENST00000263468.13	c.838A>G	p.Thr280Ala	missense_variant	6/11	1	NM_020802.4	P1
CEP126	ENST00000532529.1	c.*334A>G		3_prime_UTR_variant, NMD_transcript_variant	5/10	5
CEP126	ENST00000670091.1	c.*881A>G		3_prime_UTR_variant, NMD_transcript_variant	7/12
CEP126	ENST00000670318.1	c.*350A>G		3_prime_UTR_variant, NMD_transcript_variant	7/12

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Aug 02, 2023

The c.838A>G (p.T280A) alteration is located in exon 6 (coding exon 6) of the CEP126 gene. This alteration results from a A to G substitution at nucleotide position 838, causing the threonine (T) at amino acid position 280 to be replaced by an alanine (A). 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	0.068
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	16
Dann	Benign	0.88
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.29	N
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.040
Sift	Benign	0.070	T
Sift4G	Benign	0.18	T
Vest4		0.014
MutPred		0.18		Loss of sheet (P = 0.0228);
MVP		0.030
MPC		0.11
ClinPred		0.083	T
GERP RS		4.7
gMVP		0.072

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-101832604;