5-123346556-A-C

Position:

• chr5-123346556-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_001375405.1(CEP120):​c.2924T>G​(p.Ile975Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CEP120 NM_001375405.1 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.67

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.831
• PP5: Variant 5-123346556-A-C is Pathogenic according to our data. Variant chr5-123346556-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 446143.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-123346556-A-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP120	NM_001375405.1	c.2924T>G	p.Ile975Ser	missense_variant	20/20	ENST00000306467.10	NP_001362334.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP120	ENST00000306467.10	c.2924T>G	p.Ile975Ser	missense_variant	20/20	5	NM_001375405.1	ENSP00000303058.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

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

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 06, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	.;D;D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.4	M;M;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-4.3	D;D;D
REVEL	Pathogenic	0.71
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.044	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.97
MutPred		0.51		Gain of disorder (P = 0.0017);Gain of disorder (P = 0.0017);.;
MVP		0.60
MPC		0.51
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.80
gMVP		0.83

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: rs1554098663; hg19: chr5-122682250;