16-67828803-G-C

Variant names:

• chr16-67828803-G-C
• rs188159138
• NM_025082.4:c.1321C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_025082.4(CENPT):​c.1321C>G​(p.Pro441Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00051 in 1,596,282 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00050 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (7 hom.)
• Consequence: CENPT NM_025082.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.793
• Publications: 5 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005937159).
• BP6: Variant 16-67828803-G-C is Benign according to our data. Variant chr16-67828803-G-C is described in ClinVar as Benign. ClinVar VariationId is 3043796.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.000511 (738/1443994) while in subpopulation EAS AF = 0.0165 (654/39654). AF 95% confidence interval is 0.0154. There are 7 homozygotes in GnomAdExome4. There are 373 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 7 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.1321C>G	p.Pro441Ala	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.1321C>G	p.Pro441Ala	missense	Exon 14 of 16	ENSP00000457810.1	Q96BT3-1
	CENPT	ENST00000937858.1		c.1396C>G	p.Pro466Ala	missense	Exon 12 of 14	ENSP00000607917.1
	CENPT	ENST00000937857.1		c.1387C>G	p.Pro463Ala	missense	Exon 12 of 14	ENSP00000607916.1

Frequencies

GnomAD3 genomes AF: 0.000499 AC: 76 AN: 152170 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00101 AC: 230 AN: 227300 AF XY: 0.000951

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000370

Gnomad ASJ exome AF: 0.000339

Gnomad EAS exome AF: 0.0126

Gnomad FIN exome AF: 0.0000476

Gnomad NFE exome AF: 0.0000469

Gnomad OTH exome AF: 0.000548

GnomAD4 exome AF: 0.000511 AC: 738 AN: 1443994 Hom.: 7 Cov.: 33 AF XY: 0.000519 AC XY: 373 AN XY: 718478

African (AFR) AF: 0.00 AC: 0 AN: 32014

American (AMR) AF: 0.0000265 AC: 1 AN: 37696

Ashkenazi Jewish (ASJ) AF: 0.000357 AC: 9 AN: 25240

East Asian (EAS) AF: 0.0165 AC: 654 AN: 39654

South Asian (SAS) AF: 0.000300 AC: 25 AN: 83394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53184

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5678

European-Non Finnish (NFE) AF: 0.0000244 AC: 27 AN: 1107522

Other (OTH) AF: 0.000352 AC: 21 AN: 59612

GnomAD4 genome AF: 0.000499 AC: 76 AN: 152288 Hom.: 1 Cov.: 32 AF XY: 0.000551 AC XY: 41 AN XY: 74460

African (AFR) AF: 0.00 AC: 0 AN: 41564

American (AMR) AF: 0.0000654 AC: 1 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.0131 AC: 68 AN: 5184

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68014

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

Alfa AF: 0.000171 Hom.: 0

Bravo AF: 0.000710

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.00108 AC: 130

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	0.073
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.6
DANN	Benign	0.97
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0059	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.79
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.0070
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.25	T
Polyphen		0.094	B
Vest4		0.32
MVP		0.52
MPC		0.10
ClinPred		0.062	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.029
gMVP		0.24
Mutation Taster		=96/4	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: rs188159138; hg19: chr16-67862706; COSMIC: COSV54652085; COSMIC: COSV54652085;