rs147273517

Variant names:

• chr5-123412500-T-C
• rs147273517
• NM_001375405.1:c.362A>G

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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:3
• Conservation: PhyloP100: 4.64
• Publications: 4 publications found

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]

CEP120 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• Joubert syndrome 31

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• short-rib thoracic dysplasia 13 with or without polydactyly

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with ocular defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375405.1. 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
	CEP120	NM_001375405.1	MANE Select	c.362A>G	p.Lys121Arg	missense	Exon 4 of 20	NP_001362334.1	Q8N960-1
	CEP120	NM_153223.4		c.362A>G	p.Lys121Arg	missense	Exon 5 of 21	NP_694955.2	Q8N960-1
	CEP120	NM_001166226.2		c.284A>G	p.Lys95Arg	missense	Exon 4 of 20	NP_001159698.1	Q8N960-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP120	ENST00000306467.10	TSL:5 MANE Select	c.362A>G	p.Lys121Arg	missense	Exon 4 of 20	ENSP00000303058.6	Q8N960-1
	CEP120	ENST00000508138.5	TSL:1	n.362A>G		non_coding_transcript_exon	Exon 5 of 23	ENSP00000422234.1	D6R8Z4
	CEP120	ENST00000513565.6	TSL:1	n.362A>G		non_coding_transcript_exon	Exon 4 of 21	ENSP00000422089.2	Q8N960-3

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

GnomAD2 exomes AF: 0.00125 AC: 310 AN: 247210 AF XY: 0.000909

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 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

African (AFR) AF: 0.0165 AC: 552 AN: 33378

American (AMR) AF: 0.000856 AC: 38 AN: 44370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39594

South Asian (SAS) AF: 0.0000234 AC: 2 AN: 85632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000414 AC: 46 AN: 1110852

Other (OTH) AF: 0.000978 AC: 59 AN: 60314

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

African (AFR) AF: 0.0169 AC: 701 AN: 41590

American (AMR) AF: 0.00144 AC: 22 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68030

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00186 Hom.: 2

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Short-rib thoracic dysplasia 13 with or without polydactyly (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.18
Eigen_PC	Benign	0.018
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.6
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.043
Sift	Benign	0.39	T
Sift4G	Benign	0.46	T
Polyphen		0.042	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
Mutation Taster		=84/16	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: rs147273517; hg19: chr5-122748194;