chr11-101915399-C-A

Variant names:

• chr11-101915399-C-A
• rs1255880136
• NM_020802.4:c.115C>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.115C>A​(p.Pro39Thr) 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CEP126 NM_020802.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81

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]

ANGPTL5 (HGNC:19705): (angiopoietin like 5) Predicted to be active in collagen-containing extracellular matrix and extracellular space. [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=0.12507933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP126	NM_020802.4	c.115C>A	p.Pro39Thr	missense_variant	Exon 1 of 11	ENST00000263468.13	NP_065853.3
ANGPTL5	NM_178127.5	c.-93+620G>T		intron_variant	Intron 1 of 8	ENST00000334289.7	NP_835228.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP126	ENST00000263468.13	c.115C>A	p.Pro39Thr	missense_variant	Exon 1 of 11	1	NM_020802.4	ENSP00000263468.8
ANGPTL5	ENST00000334289.7	c.-93+620G>T		intron_variant	Intron 1 of 8	1	NM_178127.5	ENSP00000335255.3
CEP126	ENST00000670091.1	n.115C>A		non_coding_transcript_exon_variant	Exon 1 of 12			ENSP00000499679.1
CEP126	ENST00000670318.1	n.115C>A		non_coding_transcript_exon_variant	Exon 1 of 12			ENSP00000499404.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.0049	N
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.027
Sift	Uncertain	0.028	D
Sift4G	Pathogenic	0.0	D
Vest4		0.35
MutPred		0.28		Gain of catalytic residue at P39 (P = 0.003);
MVP		0.10
MPC		0.50
ClinPred		0.80	D
GERP RS		3.6
gMVP		0.076

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1255880136; hg19: chr11-101786130;