NM_020802.4:c.436C>A

Variant names:

• chr11-101948072-C-A
• NM_020802.4:c.436C>A

Variant summary

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

The NM_020802.4(CEP126):​c.436C>A​(p.Gln146Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,724 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CEP126 NM_020802.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP126	NM_020802.4	c.436C>A	p.Gln146Lys	missense_variant	Exon 4 of 11	ENST00000263468.13	NP_065853.3
CEP126	NM_001363543.2	c.-844C>A		5_prime_UTR_variant	Exon 4 of 12		NP_001350472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP126	ENST00000263468.13	c.436C>A	p.Gln146Lys	missense_variant	Exon 4 of 11	1	NM_020802.4	ENSP00000263468.8
CEP126	ENST00000532529.1	n.76C>A		non_coding_transcript_exon_variant	Exon 2 of 10	5		ENSP00000433643.1
CEP126	ENST00000670091.1	n.436C>A		non_coding_transcript_exon_variant	Exon 4 of 12			ENSP00000499679.1
CEP126	ENST00000670318.1	n.436C>A		non_coding_transcript_exon_variant	Exon 4 of 12			ENSP00000499404.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459724 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	0.0017	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	23
DANN	Uncertain	1.0
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.79	D
M_CAP	Benign	0.0054	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.2	T
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.12
Sift	Uncertain	0.013	D
Sift4G	Pathogenic	0.0	D
Vest4		0.56
MutPred		0.20		Gain of ubiquitination at Q146 (P = 0.0018);
MVP		0.45
MPC		0.61
ClinPred		0.97	D
GERP RS		5.4
gMVP		0.32

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: chr11-101818803;