16-81024737-C-T

Variant names:

• chr16-81024737-C-T
• rs200191233
• NM_001100624.3:c.656C>T

Variant summary

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

The NM_001100624.3(CENPN):​c.656C>T​(p.Thr219Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000522 in 1,609,962 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000048 (1 hom.)
• Consequence: CENPN NM_001100624.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.702
• Publications: 1 publications found

Genes affected

CENPN (HGNC:30873): (centromere protein N) The protein encoded by this gene forms part of the nucleosome-associated complex and is important for kinetochore assembly. It is bound to kinetochores during S phase and G2 and recruits other proteins to the centromere. Pseudogenes of this gene are located on chromosome 2. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

ENSG00000284512 (HGNC:):

CENPN-AS1 (HGNC:55106): (CENPN antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10678995).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100624.3. 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
	CENPN	NM_001100624.3	MANE Select	c.656C>T	p.Thr219Met	missense	Exon 8 of 11	NP_001094094.2	Q96H22-1
	CENPN	NM_001100625.3		c.656C>T	p.Thr219Met	missense	Exon 8 of 11	NP_001094095.2	Q96H22-3
	CENPN	NM_001270473.2		c.596C>T	p.Thr199Met	missense	Exon 7 of 10	NP_001257402.1	Q96H22-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPN	ENST00000305850.10	TSL:1 MANE Select	c.656C>T	p.Thr219Met	missense	Exon 8 of 11	ENSP00000305608.5	Q96H22-1
	ENSG00000284512	ENST00000640345.1	TSL:5	c.*3-132G>A		intron	N/A	ENSP00000492798.1	A0A1W2PS29
	CENPN	ENST00000393335.7	TSL:2	c.656C>T	p.Thr219Met	missense	Exon 8 of 11	ENSP00000377007.3	Q96H22-3

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 151980 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000806 AC: 20 AN: 248160 AF XY: 0.000111

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.0000559

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000708

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000480 AC: 70 AN: 1457864 Hom.: 1 Cov.: 28 AF XY: 0.0000648 AC XY: 47 AN XY: 725330

African (AFR) AF: 0.0000300 AC: 1 AN: 33364

American (AMR) AF: 0.0000899 AC: 4 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26094

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39558

South Asian (SAS) AF: 0.000222 AC: 19 AN: 85738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000361 AC: 40 AN: 1109390

Other (OTH) AF: 0.0000332 AC: 2 AN: 60248

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152098 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74328

African (AFR) AF: 0.0000482 AC: 2 AN: 41494

American (AMR) AF: 0.000131 AC: 2 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10548

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000745 AC: 9

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	0.083
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.70
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.047
Sift	Benign	0.23	T
Sift4G	Benign	0.11	T
Polyphen		0.99	D
Vest4		0.31
MutPred		0.40		Loss of relative solvent accessibility (P = 0.0404)
MVP		0.30
MPC		0.060
ClinPred		0.067	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.018
gMVP		0.29
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.20		Position offset: -22

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

Other links and lift over

dbSNP: rs200191233; hg19: chr16-81058342; COSMIC: COSV55141789; COSMIC: COSV55141789;