NM_025082.4:c.1295C>T

Variant names:

• chr16-67828829-G-A
• NM_025082.4:c.1295C>T

Variant summary

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

The NM_025082.4(CENPT):​c.1295C>T​(p.Pro432Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,430,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CENPT NM_025082.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.16
• Publications: 0 publications found

Genes affected

CENPT (HGNC:25787): (centromere protein T) The centromere is a specialized chromatin domain, present throughout the cell cycle, that acts as a platform on which the transient assembly of the kinetochore occurs during mitosis. All active centromeres are characterized by the presence of long arrays of nucleosomes in which CENPA (MIM 117139) replaces histone H3 (see MIM 601128). CENPT is an additional factor required for centromere assembly (Foltz et al., 2006 [PubMed 16622419]).[supplied by OMIM, Mar 2008]

TSNAXIP1 (HGNC:18586): (translin associated factor X interacting protein 1) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be located in perinuclear region of cytoplasm. Predicted to be active in cytoplasm. [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=0.11779702).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025082.4. 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
	CENPT	NM_025082.4	MANE Select	c.1295C>T	p.Pro432Leu	missense	Exon 14 of 16	NP_079358.3	Q96BT3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPT	ENST00000562787.6	TSL:2 MANE Select	c.1295C>T	p.Pro432Leu	missense	Exon 14 of 16	ENSP00000457810.1	Q96BT3-1
	CENPT	ENST00000937858.1		c.1370C>T	p.Pro457Leu	missense	Exon 12 of 14	ENSP00000607917.1
	CENPT	ENST00000937857.1		c.1361C>T	p.Pro454Leu	missense	Exon 12 of 14	ENSP00000607916.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1430412 Hom.: 0 Cov.: 33 AF XY: 0.00000281 AC XY: 2 AN XY: 711324

African (AFR) AF: 0.00 AC: 0 AN: 31146

American (AMR) AF: 0.00 AC: 0 AN: 32958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24392

East Asian (EAS) AF: 0.00 AC: 0 AN: 39590

South Asian (SAS) AF: 0.00 AC: 0 AN: 80886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5620

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1103792

Other (OTH) AF: 0.00 AC: 0 AN: 59058

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

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	0.093
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.2
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.10
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.0080	B
Vest4		0.25
MutPred		0.12		Gain of helix (P = 0.0349)
MVP		0.60
MPC		0.41
ClinPred		0.98	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.098
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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

hg19: chr16-67862732;