NM_025082.4:c.1265C>T

Variant names:

• chr16-67829438-G-A
• rs201434551
• NM_025082.4:c.1265C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_025082.4(CENPT):​c.1265C>T​(p.Ala422Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000228 in 1,580,862 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0012 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: CENPT NM_025082.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.08
• Publications: 2 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0049374104).
• BP6: Variant 16-67829438-G-A is Benign according to our data. Variant chr16-67829438-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3042984.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.1265C>T	p.Ala422Val	missense	Exon 13 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.1265C>T	p.Ala422Val	missense	Exon 13 of 16	ENSP00000457810.1	Q96BT3-1
	CENPT	ENST00000937858.1		c.1340C>T	p.Ala447Val	missense	Exon 11 of 14	ENSP00000607917.1
	CENPT	ENST00000937857.1		c.1331C>T	p.Ala444Val	missense	Exon 11 of 14	ENSP00000607916.1

Frequencies

GnomAD3 genomes AF: 0.00123 AC: 187 AN: 152138 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00389

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

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: 0.00

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000323 AC: 70 AN: 216984 AF XY: 0.000261

Gnomad AFR exome AF: 0.00445

Gnomad AMR exome AF: 0.000127

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000960

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000123 AC: 176 AN: 1428606 Hom.: 0 Cov.: 30 AF XY: 0.000121 AC XY: 86 AN XY: 710498

African (AFR) AF: 0.00424 AC: 132 AN: 31110

American (AMR) AF: 0.000152 AC: 5 AN: 32872

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24318

East Asian (EAS) AF: 0.00 AC: 0 AN: 39374

South Asian (SAS) AF: 0.00 AC: 0 AN: 80654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 0.0000218 AC: 24 AN: 1102548

Other (OTH) AF: 0.000254 AC: 15 AN: 58984

GnomAD4 genome AF: 0.00122 AC: 185 AN: 152256 Hom.: 2 Cov.: 32 AF XY: 0.00120 AC XY: 89 AN XY: 74448

African (AFR) AF: 0.00383 AC: 159 AN: 41554

American (AMR) AF: 0.00150 AC: 23 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000308 Hom.: 0

Bravo AF: 0.00148

ESP6500AA AF: 0.00437 AC: 18

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000372 AC: 45

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CENPT-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.0
DANN	Benign	0.89
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.1
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.023
Sift	Benign	0.23	T
Sift4G	Benign	0.18	T
Polyphen		0.0040	B
Vest4		0.094
MVP		0.27
MPC		0.091
ClinPred		0.022	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.023
gMVP		0.19
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: rs201434551; hg19: chr16-67863341; COSMIC: COSV54652532; COSMIC: COSV54652532;