16-15884106-C-G

Variant names:

• chr16-15884106-C-G
• rs1346032676
• NM_144600.4:c.128G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144600.4(CEP20):​c.128G>C​(p.Arg43Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CEP20 NM_144600.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.84
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12863684).

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.128G>C	p.Arg43Pro	missense	Exon 2 of 5	NP_653201.1	Q96NB1-1
	CEP20	NM_001304499.2		c.128G>C	p.Arg43Pro	missense	Exon 2 of 6	NP_001291428.1	I3NI25
	CEP20	NM_001304502.2		c.128G>C	p.Arg43Pro	missense	Exon 2 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.128G>C	p.Arg43Pro	missense	Exon 2 of 5	ENSP00000255759.6	Q96NB1-1
	CEP20	ENST00000929533.1		c.236G>C	p.Arg79Pro	missense	Exon 3 of 7	ENSP00000599592.1
	CEP20	ENST00000962008.1		c.128G>C	p.Arg43Pro	missense	Exon 2 of 6	ENSP00000632067.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251452 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461830 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727216

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: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111976

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

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74318

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000312 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.8
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.11
Sift	Benign	0.067	T
Sift4G	Benign	0.14	T
Polyphen		0.022	B
Vest4		0.42
MutPred		0.28		Gain of glycosylation at R43 (P = 0.0046)
MVP		0.17
MPC		0.028
ClinPred		0.29	T
GERP RS		2.7
Varity_R		0.47
gMVP		0.53
Mutation Taster		=53/47	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: rs1346032676; hg19: chr16-15977963;