14-80526895-T-A

Variant names:

• chr14-80526895-T-A
• rs773418804
• NM_152446.5:c.3046A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152446.5(CEP128):​c.3046A>T​(p.Thr1016Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1016A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CEP128 NM_152446.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.551
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.021466732).

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.3046A>T	p.Thr1016Ser	missense	Exon 23 of 25	NP_689659.2
	CEP128	NR_157142.2		n.3839A>T		non_coding_transcript_exon	Exon 23 of 25

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP128	ENST00000555265.6	TSL:5 MANE Select	c.3046A>T	p.Thr1016Ser	missense	Exon 23 of 25	ENSP00000451162.1	Q6ZU80-2
	CEP128	ENST00000281129.7	TSL:1	c.3046A>T	p.Thr1016Ser	missense	Exon 22 of 24	ENSP00000281129.3	Q6ZU80-2
	CEP128	ENST00000947694.1		c.3136A>T	p.Thr1046Ser	missense	Exon 24 of 26	ENSP00000617753.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455398 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 724484

African (AFR) AF: 0.00 AC: 0 AN: 33326

American (AMR) AF: 0.00 AC: 0 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39634

South Asian (SAS) AF: 0.00 AC: 0 AN: 85972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1106900

Other (OTH) AF: 0.00 AC: 0 AN: 60144

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.6
DANN	Benign	0.76
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.55
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.017
Sift	Benign	0.81	T
Sift4G	Benign	0.83	T
Polyphen		0.0030	B
Vest4		0.10
MutPred		0.22		Gain of MoRF binding (P = 0.1163)
MVP		0.067
MPC		0.066
ClinPred		0.023	T
GERP RS		-1.5
Varity_R		0.044
gMVP		0.046
Mutation Taster		=95/5	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: rs773418804; hg19: chr14-80993239;