chr11-101915361-C-G

Position:

• chr11-101915361-C-G

Variant summary

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

The NM_020802.4(CEP126):​c.77C>G​(p.Ala26Gly) 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. 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: 0.296

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=0.10163176).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP126	NM_020802.4	c.77C>G	p.Ala26Gly	missense_variant	1/11	ENST00000263468.13	NP_065853.3
ANGPTL5	NM_178127.5	c.-93+658G>C		intron_variant		ENST00000334289.7	NP_835228.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP126	ENST00000263468.13	c.77C>G	p.Ala26Gly	missense_variant	1/11	1	NM_020802.4	ENSP00000263468	P1
ANGPTL5	ENST00000334289.7	c.-93+658G>C		intron_variant		1	NM_178127.5	ENSP00000335255	P1
CEP126	ENST00000670091.1	c.77C>G	p.Ala26Gly	missense_variant, NMD_transcript_variant	1/12			ENSP00000499679
CEP126	ENST00000670318.1	c.77C>G	p.Ala26Gly	missense_variant, NMD_transcript_variant	1/12			ENSP00000499404

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

May 31, 2023

The c.77C>G (p.A26G) alteration is located in exon 1 (coding exon 1) of the CEP126 gene. This alteration results from a C to G substitution at nucleotide position 77, causing the alanine (A) at amino acid position 26 to be replaced by a glycine (G). 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	0.099
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Uncertain	1.0
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.0030	N
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.041
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.11
MutPred		0.26		Loss of stability (P = 0.0044);
MVP		0.14
MPC		0.48
ClinPred		0.54	D
GERP RS		1.8
gMVP		0.079

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: chr11-101786092;