16-81022615-A-C

Position:

• chr16-81022615-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001100624.3(CENPN):​c.550A>C​(p.Lys184Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CENPN NM_001100624.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.57

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35922498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPN	NM_001100624.3	c.550A>C	p.Lys184Gln	missense_variant	7/11	ENST00000305850.10	NP_001094094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPN	ENST00000305850.10	c.550A>C	p.Lys184Gln	missense_variant	7/11	1	NM_001100624.3	ENSP00000305608.5
ENSG00000284512	ENST00000640345	c.*1993T>G		3_prime_UTR_variant	6/6	5		ENSP00000492798.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.550A>C (p.K184Q) alteration is located in exon 7 (coding exon 6) of the CENPN gene. This alteration results from a A to C substitution at nucleotide position 550, causing the lysine (K) at amino acid position 184 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T;.;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.;M
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.18
Sift	Benign	0.041	D;T;T
Sift4G	Benign	0.069	T;T;T
Polyphen		0.92	P;.;.
Vest4		0.14
MutPred		0.62		Loss of ubiquitination at K184 (P = 0.0309);.;Loss of ubiquitination at K184 (P = 0.0309);
MVP		0.41
MPC		0.017
ClinPred		0.89	D
GERP RS		6.0
Varity_R		0.43
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-81056220;