rs147277049

Variant names:

• chr5-123385030-T-A
• NM_001375405.1:c.1684A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-123385030-T-A
• chr5-123385030-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001375405.1(CEP120):​c.1684A>T​(p.Thr562Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP120 NM_001375405.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.81

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16711292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP120	NM_001375405.1	c.1684A>T	p.Thr562Ser	missense_variant	Exon 11 of 20	ENST00000306467.10	NP_001362334.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP120	ENST00000306467.10	c.1684A>T	p.Thr562Ser	missense_variant	Exon 11 of 20	5	NM_001375405.1	ENSP00000303058.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Feb 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1684A>T (p.T562S) alteration is located in exon 12 (coding exon 11) of the CEP120 gene. This alteration results from a A to T substitution at nucleotide position 1684, causing the threonine (T) at amino acid position 562 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T;T;.;T
Eigen	Benign	0.086
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.71	.;T;T;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.5	L;L;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.044
Sift	Benign	0.13	T;T;T;T
Sift4G	Benign	0.33	T;T;T;T
Polyphen		0.078	B;B;.;.
Vest4		0.26
MutPred		0.22		Gain of disorder (P = 0.0332);Gain of disorder (P = 0.0332);.;.;
MVP		0.29
MPC		0.067
ClinPred		0.49	T
GERP RS		5.6
Varity_R		0.23
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: -13

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-122720724;