chr16-67828791-G-A

Variant names:

• chr16-67828791-G-A
• rs371608100
• NM_025082.4:c.1333C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_025082.4(CENPT):​c.1333C>T​(p.Arg445Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000324 in 1,600,134 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R445P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00034 (0 hom.)
• Consequence: CENPT NM_025082.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10637763).

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.1333C>T	p.Arg445Trp	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.1333C>T	p.Arg445Trp	missense	Exon 14 of 16	ENSP00000457810.1	Q96BT3-1
	CENPT	ENST00000937858.1		c.1408C>T	p.Arg470Trp	missense	Exon 12 of 14	ENSP00000607917.1
	CENPT	ENST00000937857.1		c.1399C>T	p.Arg467Trp	missense	Exon 12 of 14	ENSP00000607916.1

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000179 AC: 42 AN: 234428 AF XY: 0.000141

Gnomad AFR exome AF: 0.000133

Gnomad AMR exome AF: 0.0000341

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000472

Gnomad NFE exome AF: 0.000340

Gnomad OTH exome AF: 0.000176

GnomAD4 exome AF: 0.000340 AC: 492 AN: 1447826 Hom.: 0 Cov.: 33 AF XY: 0.000310 AC XY: 223 AN XY: 720452

African (AFR) AF: 0.0000929 AC: 3 AN: 32296

American (AMR) AF: 0.0000510 AC: 2 AN: 39232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25428

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 84102

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.000429 AC: 476 AN: 1108456

Other (OTH) AF: 0.000167 AC: 10 AN: 59756

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74472

African (AFR) AF: 0.0000241 AC: 1 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000410 Hom.: 0

Bravo AF: 0.000193

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000489 AC: 4

ExAC AF: 0.000166 AC: 20

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.15
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.078	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.4
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.10
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.020	D
Polyphen		0.99	D
Vest4		0.35
MVP		0.64
MPC		0.42
ClinPred		0.19	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.059
gMVP		0.41
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs371608100; hg19: chr16-67862694;