NM_152446.5:c.2759T>G

Variant names:

• chr14-80743122-A-C
• rs376263744
• NM_152446.5:c.2759T>G

Variant summary

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

The NM_152446.5(CEP128):​c.2759T>G​(p.Ile920Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,520 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CEP128 NM_152446.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.36

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP128	NM_152446.5	c.2759T>G	p.Ile920Arg	missense_variant	Exon 19 of 25	ENST00000555265.6	NP_689659.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP128	ENST00000555265.6	c.2759T>G	p.Ile920Arg	missense_variant	Exon 19 of 25	5	NM_152446.5	ENSP00000451162.1
CEP128	ENST00000281129.7	c.2759T>G	p.Ile920Arg	missense_variant	Exon 18 of 24	1		ENSP00000281129.3
CEP128	ENST00000554728.1	c.362T>G	p.Ile121Arg	missense_variant	Exon 3 of 3	2		ENSP00000451273.1
CEP128	ENST00000554502.5	n.1832T>G		non_coding_transcript_exon_variant	Exon 8 of 15	2		ENSP00000451319.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 250984 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135634

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461520 Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6 AN XY: 727054

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T;.;T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.50	D;D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.1	M;M;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.056	T;T;D
Polyphen		1.0	D;D;.
Vest4		0.82
MutPred		0.25		Gain of catalytic residue at L916 (P = 0.002);Gain of catalytic residue at L916 (P = 0.002);.;
MVP		0.52
MPC		0.56
ClinPred		0.92	D
GERP RS		5.3
Varity_R		0.61
gMVP		0.65

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: rs376263744; hg19: chr14-81209466;