chr16-15867447-T-C

Variant names:

• chr16-15867447-T-C
• rs747771923
• NM_144600.4:c.518A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144600.4(CEP20):​c.518A>G​(p.Asn173Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000827 in 1,596,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000083 (0 hom.)
• Consequence: CEP20 NM_144600.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026670903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP20	NM_144600.4	c.518A>G	p.Asn173Ser	missense_variant	Exon 5 of 5	ENST00000255759.11	NP_653201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP20	ENST00000255759.11	c.518A>G	p.Asn173Ser	missense_variant	Exon 5 of 5	1	NM_144600.4	ENSP00000255759.6

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152196 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: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000154 AC: 38 AN: 246088 AF XY: 0.000128

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: 0.000320

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.0000831 AC: 120 AN: 1444216 Hom.: 0 Cov.: 29 AF XY: 0.0000808 AC XY: 58 AN XY: 717846

African (AFR) AF: 0.00 AC: 0 AN: 33124

American (AMR) AF: 0.00 AC: 0 AN: 43200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25706

East Asian (EAS) AF: 0.00 AC: 0 AN: 39352

South Asian (SAS) AF: 0.00 AC: 0 AN: 83230

European-Finnish (FIN) AF: 0.000133 AC: 7 AN: 52740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5548

European-Non Finnish (NFE) AF: 0.0000962 AC: 106 AN: 1101820

Other (OTH) AF: 0.000118 AC: 7 AN: 59496

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152196 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41452

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

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000138 Hom.: 0

Bravo AF: 0.0000340

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000247 AC: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 23, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.518A>G (p.N173S) alteration is located in exon 5 (coding exon 5) of the FOPNL gene. This alteration results from a A to G substitution at nucleotide position 518, causing the asparagine (N) at amino acid position 173 to be replaced by a serine (S). 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	0.068
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.7
DANN	Benign	0.89
DEOGEN2	Benign	0.0057	T;.;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.69	T;T;T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.027	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N;.;.;.
PhyloP100		1.1
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.61	N;.;.;.
REVEL	Benign	0.036
Sift	Benign	0.44	T;.;.;.
Sift4G	Benign	0.24	T;D;T;T
Polyphen		0.0010	B;.;.;.
Vest4		0.035
MVP		0.030
MPC		0.015
ClinPred		0.028	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.042
gMVP		0.050
Mutation Taster		=95/5	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: rs747771923; hg19: chr16-15961304;