rs1887546330

Variant names:

• chr14-80497574-T-C
• rs1887546330
• NM_152446.5:c.3190A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152446.5(CEP128):​c.3190A>G​(p.Lys1064Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CEP128 NM_152446.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.84
• Publications: 0 publications found

Genes affected

CEP128 (HGNC:20359): (centrosomal protein 128) Involved in protein localization. Located in centriole and spindle pole. Part of centriolar subdistal appendage. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15102741).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152446.5. 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
	CEP128	NM_152446.5	MANE Select	c.3190A>G	p.Lys1064Glu	missense	Exon 25 of 25	NP_689659.2
	CEP128	NR_157142.2		n.3983A>G		non_coding_transcript_exon	Exon 25 of 25

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP128	ENST00000555265.6	TSL:5 MANE Select	c.3190A>G	p.Lys1064Glu	missense	Exon 25 of 25	ENSP00000451162.1	Q6ZU80-2
	CEP128	ENST00000281129.7	TSL:1	c.3190A>G	p.Lys1064Glu	missense	Exon 24 of 24	ENSP00000281129.3	Q6ZU80-2
	CEP128	ENST00000947694.1		c.3280A>G	p.Lys1094Glu	missense	Exon 26 of 26	ENSP00000617753.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.023
Eigen_PC	Benign	0.077
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		1.8
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.032
Sift	Benign	0.046	D
Sift4G	Benign	0.097	T
Polyphen		0.51	P
Vest4		0.23
MutPred		0.25		Gain of catalytic residue at V1067 (P = 0.0098)
MVP		0.25
MPC		0.15
ClinPred		0.67	D
GERP RS		3.7
Varity_R		0.25
gMVP		0.098
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1887546330; hg19: chr14-80963917;