11-101961859-C-T

Variant names:

• chr11-101961859-C-T
• rs11225089
• NM_020802.4:c.824C>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.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. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP126 NM_020802.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 15 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=0.14134246).

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.824C>T	p.Ser275Phe	missense	Exon 6 of 11	NP_065853.3	Q9P2H0
	CEP126	NM_001363543.2		c.227C>T	p.Ser76Phe	missense	Exon 7 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.824C>T	p.Ser275Phe	missense	Exon 6 of 11	ENSP00000263468.8	Q9P2H0
	CEP126	ENST00000931861.1		c.824C>T	p.Ser275Phe	missense	Exon 6 of 11	ENSP00000601920.1
	CEP126	ENST00000532529.1	TSL:5	n.*320C>T		non_coding_transcript_exon	Exon 5 of 10	ENSP00000433643.1	H0YDI0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 930

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		2.0
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
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs11225089; hg19: chr11-101832590;