4-67514497-G-T

Position:

• chr4-67514497-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001812.4(CENPC):​c.1021C>A​(p.Leu341Ile) 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. 14/20 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. L341F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CENPC NM_001812.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.550

Genes affected

CENPC (HGNC:1854): (centromere protein C) Centromere protein C 1 is a centromere autoantigen and a component of the inner kinetochore plate. The protein is required for maintaining proper kinetochore size and a timely transition to anaphase. A putative pseudogene exists on chromosome 12. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12177372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPC	NM_001812.4	c.1021C>A	p.Leu341Ile	missense_variant	8/19	ENST00000273853.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPC	ENST00000273853.11	c.1021C>A	p.Leu341Ile	missense_variant	8/19	1	NM_001812.4	P1
CENPC	ENST00000510189.5	n.1169C>A		non_coding_transcript_exon_variant	8/14	1
CENPC	ENST00000506882.5	c.1021C>A	p.Leu341Ile	missense_variant, NMD_transcript_variant	8/20	1
CENPC	ENST00000513216.5	c.742C>A	p.Leu248Ile	missense_variant, NMD_transcript_variant	4/15	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.0
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.042
Sift	Benign	0.22	T
Sift4G	Benign	0.19	T
Polyphen		0.76	P
Vest4		0.13
MutPred		0.24		Gain of catalytic residue at L341 (P = 0.0685);
MVP		0.43
MPC		0.055
ClinPred		0.13	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.033
gMVP		0.024

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

Publications

LitVar

Other links and lift over

dbSNP: rs11250; hg19: chr4-68380215;