16-15888570-C-T

Variant names:

• chr16-15888570-C-T
• rs776955193
• NM_144600.4:c.16G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_144600.4(CEP20):​c.16G>A​(p.Glu6Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. E6G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CEP20 NM_144600.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96
• Publications: 0 publications found

Genes affected

CEP20 (HGNC:26435): (centrosomal protein 20) Enables identical protein binding activity. Involved in cilium assembly. Located in centriolar satellite and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.768

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144600.4. 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
	CEP20	NM_144600.4	MANE Select	c.16G>A	p.Glu6Lys	missense	Exon 1 of 5	NP_653201.1	Q96NB1-1
	CEP20	NM_001304499.2		c.16G>A	p.Glu6Lys	missense	Exon 1 of 6	NP_001291428.1	I3NI25
	CEP20	NM_001304502.2		c.16G>A	p.Glu6Lys	missense	Exon 1 of 5	NP_001291431.1	I3L4V2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP20	ENST00000255759.11	TSL:1 MANE Select	c.16G>A	p.Glu6Lys	missense	Exon 1 of 5	ENSP00000255759.6	Q96NB1-1
	CEP20	ENST00000929533.1		c.16G>A	p.Glu6Lys	missense	Exon 1 of 7	ENSP00000599592.1
	CEP20	ENST00000962008.1		c.16G>A	p.Glu6Lys	missense	Exon 1 of 6	ENSP00000632067.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.0
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.019	D
Polyphen		0.99	D
Vest4		0.70
MutPred		0.56		Gain of MoRF binding (P = 0)
MVP		0.17
MPC		0.11
ClinPred		0.99	D
GERP RS		5.6
PromoterAI		-0.18	Neutral
Varity_R		0.50
gMVP		0.68
Mutation Taster		=66/34	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: rs776955193; hg19: chr16-15982427;