5-123383042-G-C

Variant names:

• chr5-123383042-G-C
• rs6595440
• NM_001375405.1:c.1804C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001375405.1(CEP120):​c.1804C>G​(p.Leu602Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,557,710 control chromosomes in the GnomAD database, including 138,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L602L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.40 (12285 hom., cov: 33)
  • Exomes 𝑓: 0.42 (126162 hom.)
• Consequence: CEP120 NM_001375405.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.83
• Publications: 41 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=0.0030404925).
• BP6: Variant 5-123383042-G-C is Benign according to our data. Variant chr5-123383042-G-C is described in ClinVar as Benign. ClinVar VariationId is 1167917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

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.1804C>G	p.Leu602Val	missense	Exon 12 of 20	NP_001362334.1	Q8N960-1
	CEP120	NM_153223.4		c.1804C>G	p.Leu602Val	missense	Exon 13 of 21	NP_694955.2	Q8N960-1
	CEP120	NM_001166226.2		c.1726C>G	p.Leu576Val	missense	Exon 12 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.1804C>G	p.Leu602Val	missense	Exon 12 of 20	ENSP00000303058.6	Q8N960-1
	CEP120	ENST00000508138.5	TSL:1	n.*1376C>G		non_coding_transcript_exon	Exon 15 of 23	ENSP00000422234.1	D6R8Z4
	CEP120	ENST00000513565.6	TSL:1	n.*1014C>G		non_coding_transcript_exon	Exon 12 of 21	ENSP00000422089.2	Q8N960-3

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60719 AN: 151912 Hom.: 12282 Cov.: 33

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.424

GnomAD2 exomes AF: 0.421 AC: 103140 AN: 245190 AF XY: 0.425

Gnomad AFR exome AF: 0.316

Gnomad AMR exome AF: 0.390

Gnomad ASJ exome AF: 0.347

Gnomad EAS exome AF: 0.478

Gnomad FIN exome AF: 0.441

Gnomad NFE exome AF: 0.428

Gnomad OTH exome AF: 0.413

GnomAD4 exome AF: 0.421 AC: 591916 AN: 1405680 Hom.: 126162 Cov.: 26 AF XY: 0.423 AC XY: 297017 AN XY: 701742

African (AFR) AF: 0.317 AC: 10270 AN: 32408

American (AMR) AF: 0.394 AC: 17252 AN: 43738

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 8871 AN: 25630

East Asian (EAS) AF: 0.470 AC: 18486 AN: 39316

South Asian (SAS) AF: 0.461 AC: 38642 AN: 83884

European-Finnish (FIN) AF: 0.442 AC: 23484 AN: 53114

Middle Eastern (MID) AF: 0.471 AC: 2648 AN: 5626

European-Non Finnish (NFE) AF: 0.421 AC: 448097 AN: 1063580

Other (OTH) AF: 0.414 AC: 24166 AN: 58384

GnomAD4 genome AF: 0.400 AC: 60747 AN: 152030 Hom.: 12285 Cov.: 33 AF XY: 0.401 AC XY: 29796 AN XY: 74302

African (AFR) AF: 0.321 AC: 13310 AN: 41462

American (AMR) AF: 0.410 AC: 6260 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1261 AN: 3470

East Asian (EAS) AF: 0.478 AC: 2474 AN: 5174

South Asian (SAS) AF: 0.467 AC: 2252 AN: 4824

European-Finnish (FIN) AF: 0.451 AC: 4760 AN: 10554

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29107 AN: 67956

Other (OTH) AF: 0.425 AC: 900 AN: 2116

Alfa AF: 0.377 Hom.: 3299

Bravo AF: 0.394

TwinsUK AF: 0.416 AC: 1542

ALSPAC AF: 0.430 AC: 1656

ESP6500AA AF: 0.322 AC: 1415

ESP6500EA AF: 0.427 AC: 3666

ExAC AF: 0.420 AC: 50953

Asia WGS AF: 0.470 AC: 1633 AN: 3476

EpiCase AF: 0.431

EpiControl AF: 0.427

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (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	0.17
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.8
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.20
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.33
MPC		0.43
ClinPred		0.023	T
GERP RS		1.9
Varity_R		0.34
gMVP		0.52
Mutation Taster		=95/5	polymorphism (auto)

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: rs6595440; hg19: chr5-122718736; COSMIC: COSV60264427;