NM_020802.4:c.532G>C

Variant names:

• chr11-101958193-G-C
• rs11225086
• NM_020802.4:c.532G>C

Variant summary

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

The NM_020802.4(CEP126):​c.532G>C​(p.Ala178Pro) 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. 13/19 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. A178T) 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: -0.368

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=0.045071244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP126	NM_020802.4	c.532G>C	p.Ala178Pro	missense_variant	Exon 5 of 11	ENST00000263468.13	NP_065853.3
CEP126	NM_001363543.2	c.-66G>C		5_prime_UTR_variant	Exon 6 of 12		NP_001350472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP126	ENST00000263468.13	c.532G>C	p.Ala178Pro	missense_variant	Exon 5 of 11	1	NM_020802.4	ENSP00000263468.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.0
DANN	Uncertain	0.98
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.042	N
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.94	T
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.021
Sift	Benign	0.24	T
Sift4G	Benign	0.12	T
Vest4		0.074
MutPred		0.16		Gain of glycosylation at A178 (P = 0.0174);
MVP		0.030
MPC		0.15
ClinPred		0.16	T
GERP RS		-3.4
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs11225086; hg19: chr11-101828924;