rs147273517

Positions:

• chr5-123412500-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001375405.1(CEP120):​c.362A>G​(p.Lys121Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000888 in 1,611,802 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (8 hom., cov: 33)
  • Exomes 𝑓: 0.00048 (5 hom.)
• Consequence: CEP120 NM_001375405.1 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.64

Genes affected

CEP120 (HGNC:26690): (centrosomal protein 120) This gene encodes a protein that functions in the microtubule-dependent coupling of the nucleus and the centrosome. A similar protein in mouse plays a role in both interkinetic nuclear migration, which is a characteristic pattern of nuclear movement in neural progenitors, and in neural progenitor self-renewal. Mutations in this gene are predicted to result in neurogenic defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005660236).
• BP6: Variant 5-123412500-T-C is Benign according to our data. Variant chr5-123412500-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 476166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0048 (732/152374) while in subpopulation AFR AF= 0.0169 (701/41590). AF 95% confidence interval is 0.0158. There are 8 homozygotes in gnomad4. There are 372 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP120	NM_001375405.1	c.362A>G	p.Lys121Arg	missense_variant	4/20	ENST00000306467.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP120	ENST00000306467.10	c.362A>G	p.Lys121Arg	missense_variant	4/20	5	NM_001375405.1	P1

Frequencies

GnomAD3 genomes AF: 0.00470 AC: 715 AN: 152256 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

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: 0.00239

GnomAD3 exomes AF: 0.00125 AC: 310 AN: 247210 Hom.: 3 AF XY: 0.000909 AC XY: 122 AN XY: 134242

Gnomad AFR exome AF: 0.0177

Gnomad AMR exome AF: 0.000802

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000444

Gnomad OTH exome AF: 0.000843

GnomAD4 exome AF: 0.000479 AC: 699 AN: 1459428 Hom.: 5 Cov.: 30 AF XY: 0.000431 AC XY: 313 AN XY: 725970

Gnomad4 AFR exome AF: 0.0165

Gnomad4 AMR exome AF: 0.000856

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000414

Gnomad4 OTH exome AF: 0.000978

GnomAD4 genome AF: 0.00480 AC: 732 AN: 152374 Hom.: 8 Cov.: 33 AF XY: 0.00499 AC XY: 372 AN XY: 74524

Gnomad4 AFR AF: 0.0169

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.000894 Hom.: 0

Bravo AF: 0.00526

ESP6500AA AF: 0.0171 AC: 62

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00142 AC: 172

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000110

EpiControl AF: 0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 22, 2021

- -

Short-rib thoracic dysplasia 13 with or without polydactyly Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T;.;T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	0.018
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	.;T;T;T;T
MetaRNN	Benign	0.0057	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L;L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.1	N;N;N;N;N
REVEL	Benign	0.043
Sift	Benign	0.39	T;T;T;T;T
Sift4G	Benign	0.46	T;T;T;T;.
Polyphen		0.042	B;B;.;.;.
Vest4		0.26
MVP		0.53
MPC		0.074
ClinPred		0.019	T
GERP RS		4.7
Varity_R		0.29
gMVP		0.33

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

LitVar

Other links and lift over

dbSNP: rs147273517; hg19: chr5-122748194;