rs3743733

Variant names:

• chr16-67829548-T-C
• rs3743733
• NM_025082.4:c.1187-32A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_025082.4(CENPT):​c.1187-32A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,566,176 control chromosomes in the GnomAD database, including 185,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (28552 hom., cov: 31)
  • Exomes 𝑓: 0.46 (156663 hom.)
• Consequence: CENPT NM_025082.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.332
• Publications: 22 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-67829548-T-C is Benign according to our data. Variant chr16-67829548-T-C is described in ClinVar as Benign. ClinVar VariationId is 1209720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

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.1187-32A>G		intron	N/A	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.1187-32A>G		intron	N/A	ENSP00000457810.1	Q96BT3-1
	CENPT	ENST00000937858.1		c.1262-32A>G		intron	N/A	ENSP00000607917.1
	CENPT	ENST00000937857.1		c.1253-32A>G		intron	N/A	ENSP00000607916.1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87696 AN: 151860 Hom.: 28501 Cov.: 31

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.553

GnomAD2 exomes AF: 0.484 AC: 107630 AN: 222164 AF XY: 0.485

Gnomad AFR exome AF: 0.897

Gnomad AMR exome AF: 0.425

Gnomad ASJ exome AF: 0.529

Gnomad EAS exome AF: 0.140

Gnomad FIN exome AF: 0.499

Gnomad NFE exome AF: 0.464

Gnomad OTH exome AF: 0.496

GnomAD4 exome AF: 0.460 AC: 650878 AN: 1414196 Hom.: 156663 Cov.: 24 AF XY: 0.464 AC XY: 327014 AN XY: 705092

African (AFR) AF: 0.907 AC: 28355 AN: 31268

American (AMR) AF: 0.438 AC: 15808 AN: 36066

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 13406 AN: 24770

East Asian (EAS) AF: 0.146 AC: 5773 AN: 39408

South Asian (SAS) AF: 0.570 AC: 46861 AN: 82196

European-Finnish (FIN) AF: 0.495 AC: 26208 AN: 52960

Middle Eastern (MID) AF: 0.606 AC: 3370 AN: 5562

European-Non Finnish (NFE) AF: 0.446 AC: 482802 AN: 1083466

Other (OTH) AF: 0.484 AC: 28295 AN: 58500

GnomAD4 genome AF: 0.578 AC: 87804 AN: 151980 Hom.: 28552 Cov.: 31 AF XY: 0.577 AC XY: 42859 AN XY: 74274

African (AFR) AF: 0.888 AC: 36831 AN: 41470

American (AMR) AF: 0.489 AC: 7477 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1894 AN: 3472

East Asian (EAS) AF: 0.149 AC: 767 AN: 5162

South Asian (SAS) AF: 0.564 AC: 2713 AN: 4810

European-Finnish (FIN) AF: 0.510 AC: 5401 AN: 10582

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30908 AN: 67888

Other (OTH) AF: 0.558 AC: 1180 AN: 2114

Alfa AF: 0.502 Hom.: 31694

Bravo AF: 0.583

Asia WGS AF: 0.455 AC: 1586 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Short stature and microcephaly with genital anomalies (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.41
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

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: rs3743733; hg19: chr16-67863451; COSMIC: COSV54649504; COSMIC: COSV54649504;