rs61744334

chr5-123378350-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.2182A>G(p.Ser728Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,606,672 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0070 (10 hom., cov: 30)
  • Exomes 𝑓: 0.00078 (9 hom.)
• Consequence: CEP120 NM_001375405.1 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.01

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=0.0023715496).
• BP6: Variant 5-123378350-T-C is Benign according to our data. Variant chr5-123378350-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 476163.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 = 0.00704 (1069/151808) while in subpopulation AFR AF= 0.0246 (1017/41382). AF 95% confidence interval is 0.0233. There are 10 homozygotes in gnomad4. There are 554 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP120	NM_001375405.1	c.2182A>G	p.Ser728Gly	missense_variant	15/20	ENST00000306467.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP120	ENST00000306467.10	c.2182A>G	p.Ser728Gly	missense_variant	15/20	5	NM_001375405.1	P1

Frequencies

GnomAD3 genomes AF: 0.00692 AC: 1050 AN: 151688 Hom.: 9 Cov.: 30

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00184

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: 0.000265

Gnomad OTH AF: 0.00288

GnomAD3 exomes AF: 0.00186 AC: 456 AN: 245084 Hom.: 7 AF XY: 0.00134 AC XY: 178 AN XY: 132690

Gnomad AFR exome AF: 0.0244

Gnomad AMR exome AF: 0.00146

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: 0.000116

Gnomad OTH exome AF: 0.00168

GnomAD4 exome AF: 0.000782 AC: 1138 AN: 1454864 Hom.: 9 Cov.: 31 AF XY: 0.000734 AC XY: 531 AN XY: 723886

Gnomad4 AFR exome AF: 0.0243

Gnomad4 AMR exome AF: 0.00160

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000352

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000151

Gnomad4 OTH exome AF: 0.00150

GnomAD4 genome AF: 0.00704 AC: 1069 AN: 151808 Hom.: 10 Cov.: 30 AF XY: 0.00747 AC XY: 554 AN XY: 74184

Gnomad4 AFR AF: 0.0246

Gnomad4 AMR AF: 0.00184

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.00142 Hom.: 2

Bravo AF: 0.00788

ESP6500AA AF: 0.0238 AC: 105

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00231 AC: 280

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000222

EpiControl AF: 0.000241

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

May 10, 2022

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 05, 2020

- -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	14
Dann	Uncertain	0.98
DEOGEN2	Benign	0.0078	T;T;.;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.59	D
MetaRNN	Benign	0.0024	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.7	N;N;N;N
REVEL	Benign	0.024
Sift	Benign	0.35	T;T;T;T
Sift4G	Benign	0.37	T;T;T;T
Polyphen		0.0010	B;B;.;.
Vest4		0.13
MVP		0.21
MPC		0.067
ClinPred		0.0080	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.056
gMVP		0.070

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: rs61744334; hg19: chr5-122714044;