rs1580615500

Variant names:

• chr5-123346656-C-T
• rs1580615500
• NM_001375405.1:c.2824G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001375405.1(CEP120):​c.2824G>A​(p.Asp942Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D942D) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: CEP120 NM_001375405.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.51
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17301527).

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.2824G>A	p.Asp942Asn	missense	Exon 20 of 20	NP_001362334.1	Q8N960-1
	CEP120	NM_153223.4		c.2824G>A	p.Asp942Asn	missense	Exon 21 of 21	NP_694955.2	Q8N960-1
	CEP120	NM_001166226.2		c.2746G>A	p.Asp916Asn	missense	Exon 20 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.2824G>A	p.Asp942Asn	missense	Exon 20 of 20	ENSP00000303058.6	Q8N960-1
	CEP120	ENST00000508138.5	TSL:1	n.*2396G>A		non_coding_transcript_exon	Exon 23 of 23	ENSP00000422234.1	D6R8Z4
	CEP120	ENST00000513565.6	TSL:1	n.*2228G>A		non_coding_transcript_exon	Exon 21 of 21	ENSP00000422089.2	Q8N960-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251076 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461674 Hom.: 0 Cov.: 34 AF XY: 0.0000110 AC XY: 8 AN XY: 727132

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.000328 AC: 13 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111922

Other (OTH) AF: 0.0000166 AC: 1 AN: 60388

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Short-rib thoracic dysplasia 13 with or without polydactyly (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		6.5
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.13
Sift	Benign	0.20	T
Sift4G	Benign	0.27	T
Polyphen		0.79	P
Vest4		0.31
MutPred		0.30		Gain of helix (P = 0.062)
MVP		0.23
MPC		0.15
ClinPred		0.78	D
GERP RS		5.4
Varity_R		0.15
gMVP		0.26
Mutation Taster		=68/32	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: rs1580615500; hg19: chr5-122682350;