rs199499043

Variant names:

• chr16-81014142-C-A
• rs199499043
• NM_001100624.3:c.178C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-81014142-C-A
• chr16-81014142-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001100624.3(CENPN):​c.178C>A​(p.Arg60Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R60C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CENPN NM_001100624.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 0 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]

CMC2 (HGNC:24447): (C-X9-C motif containing 2) Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030816317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPN	NM_001100624.3	c.178C>A	p.Arg60Ser	missense_variant	Exon 3 of 11	ENST00000305850.10	NP_001094094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPN	ENST00000305850.10	c.178C>A	p.Arg60Ser	missense_variant	Exon 3 of 11	1	NM_001100624.3	ENSP00000305608.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460626 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 726736

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111054

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.018
DANN	Benign	0.53
DEOGEN2	Benign	0.0056	T;.;.;.;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.37	T;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.031	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;L;L;L;.
PhyloP100		-1.2
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.1	N;N;N;N;N;N
REVEL	Benign	0.012
Sift	Benign	1.0	T;T;T;T;T;T
Sift4G	Benign	0.66	T;T;T;T;T;T
Polyphen		0.0070	B;B;.;.;.;.
Vest4		0.20
MutPred		0.31		Gain of disorder (P = 0.0443);Gain of disorder (P = 0.0443);Gain of disorder (P = 0.0443);Gain of disorder (P = 0.0443);Gain of disorder (P = 0.0443);Gain of disorder (P = 0.0443);
MVP		0.040
MPC		0.018
ClinPred		0.029	T
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.25
gMVP		0.17
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs199499043; hg19: chr16-81047747;