rs3742165

chr13-24892817-T-Achr13-24892817-T-Cchr13-24892817-T-G

Variant summary

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

The NM_018451.5(CENPJ):c.3042A>T(p.Glu1014Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E1014E) has been classified as Benign.

• Frequency: Genomes: not found (cov: 29)
• Consequence: CENPJ NM_018451.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210

Genes affected

CENPJ (HGNC:17272): (centromere protein J) This gene encodes a protein that belongs to the centromere protein family. During cell division, this protein plays a structural role in the maintenance of centrosome integrity and normal spindle morphology, and it is involved in microtubule disassembly at the centrosome. This protein can function as a transcriptional coactivator in the Stat5 signaling pathway, and also as a coactivator of NF-kappaB-mediated transcription, likely via its interaction with the coactivator p300/CREB-binding protein. Mutations in this gene are associated with primary autosomal recessive microcephaly, a disorder characterized by severely reduced brain size and cognitive disability. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPJ	NM_018451.5	c.3042A>T	p.Glu1014Asp	missense_variant	10/17	ENST00000381884.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPJ	ENST00000381884.9	c.3042A>T	p.Glu1014Asp	missense_variant	10/17	1	NM_018451.5	P1
CENPJ	ENST00000418179.1	c.288A>T	p.Glu96Asp	missense_variant	3/4	1
CENPJ	ENST00000616936.4	c.3042A>T	p.Glu1014Asp	missense_variant, NMD_transcript_variant	10/16	1
CENPJ	ENST00000545981.6	c.3042A>T	p.Glu1014Asp	missense_variant, NMD_transcript_variant	10/18	2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	23
Dann	Uncertain	1.0
Eigen	Benign	0.18
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.8	L;L;.
MutationTaster	Benign	0.0054	P;P
PrimateAI	Benign	0.48	T
Sift4G	Benign	0.095	T;D;D
Polyphen		1.0	.;D;.
Vest4		0.79
MutPred		0.14		Gain of catalytic residue at S1019 (P = 0.0608);Gain of catalytic residue at S1019 (P = 0.0608);Gain of catalytic residue at S1019 (P = 0.0608);
MVP		0.61
MPC		0.54
ClinPred		0.94	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.069

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: rs3742165; hg19: chr13-25466955;