rs200591412

Variant names:

• chr16-15879861-T-C
• rs200591412
• NM_144600.4:c.254A>G

Variant summary

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

The NM_144600.4(CEP20):​c.254A>G​(p.Asp85Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000028 in 1,569,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: CEP20 NM_144600.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.65
• 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 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
CEP20	NM_144600.4	c.254A>G	p.Asp85Gly	missense_variant	Exon 3 of 5	ENST00000255759.11	NP_653201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP20	ENST00000255759.11	c.254A>G	p.Asp85Gly	missense_variant	Exon 3 of 5	1	NM_144600.4	ENSP00000255759.6

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152270 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000245 AC: 5 AN: 203846 AF XY: 0.0000268

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: 0.0000510

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000268 AC: 38 AN: 1417544 Hom.: 0 Cov.: 29 AF XY: 0.0000283 AC XY: 20 AN XY: 705580

African (AFR) AF: 0.00 AC: 0 AN: 29436

American (AMR) AF: 0.0000312 AC: 1 AN: 32092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25080

East Asian (EAS) AF: 0.00 AC: 0 AN: 35842

South Asian (SAS) AF: 0.00 AC: 0 AN: 80280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.0000319 AC: 35 AN: 1098070

Other (OTH) AF: 0.0000342 AC: 2 AN: 58556

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152270 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74394

African (AFR) AF: 0.00 AC: 0 AN: 41470

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68052

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.0000330 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.254A>G (p.D85G) alteration is located in exon 3 (coding exon 3) of the FOPNL gene. This alteration results from a A to G substitution at nucleotide position 254, causing the aspartic acid (D) at amino acid position 85 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	0.29
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.;T;T;T;T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.28	T;T;T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.3	M;.;.;.;.;.
PhyloP100		4.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-4.7	D;.;.;.;.;.
REVEL	Benign	0.14
Sift	Benign	0.078	T;.;.;.;.;.
Sift4G	Benign	0.083	T;T;T;T;T;.
Polyphen		0.33	B;.;.;.;.;.
Vest4		0.47
MutPred		0.34		Loss of stability (P = 0.0837);.;.;Loss of stability (P = 0.0837);.;.;
MVP		0.34
MPC		0.034
ClinPred		0.48	T
GERP RS		5.9
Varity_R		0.47
gMVP		0.45
Mutation Taster		=17/83	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.26		Position offset: 27

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200591412; hg19: chr16-15973718;