16-67833836-GCT-ACG

Variant names:

• chr16-67833836-GCT-ACG
• NM_025082.4:c.22_24delAGCinsCGT
• CENPT p.Ser8Arg

Variant summary

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

The NM_025082.4(CENPT):​c.22_24delAGCinsCGT​(p.Ser8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S8G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CENPT NM_025082.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158
• 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]

CENPT Gene-Disease associations (from GenCC):

• short stature and microcephaly with genital anomalies

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.22_24delAGCinsCGT	p.Ser8Arg	missense	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.22_24delAGCinsCGT	p.Ser8Arg	missense	N/A	ENSP00000457810.1	Q96BT3-1
	CENPT	ENST00000937858.1		c.22_24delAGCinsCGT	p.Ser8Arg	missense	N/A	ENSP00000607917.1
	CENPT	ENST00000937857.1		c.22_24delAGCinsCGT	p.Ser8Arg	missense	N/A	ENSP00000607916.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-67867739;