11-101961859-C-T

Variant summary

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

The NM_020802.4(CEP126):c.824C>T(p.Ser275Phe) 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. 12/19 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. S275Y) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP126 NM_020802.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04

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=0.14134246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP126	NM_020802.4	c.824C>T	p.Ser275Phe	missense_variant	6/11	ENST00000263468.13
CEP126	NM_001363543.2	c.227C>T	p.Ser76Phe	missense_variant	7/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP126	ENST00000263468.13	c.824C>T	p.Ser275Phe	missense_variant	6/11	1	NM_020802.4	P1
CEP126	ENST00000532529.1	c.*320C>T		3_prime_UTR_variant, NMD_transcript_variant	5/10	5
CEP126	ENST00000670091.1	c.*867C>T		3_prime_UTR_variant, NMD_transcript_variant	7/12
CEP126	ENST00000670318.1	c.*336C>T		3_prime_UTR_variant, NMD_transcript_variant	7/12

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	16
Dann	Uncertain	1.0
Eigen	Benign	-0.026
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.18	N
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.087
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Vest4		0.21
MutPred		0.17		Loss of disorder (P = 0.0094);
MVP		0.26
MPC		0.50
ClinPred		0.91	D
GERP RS		3.9
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs11225089; hg19: chr11-101832590;