13-24909999-G-C

Variant names:

• chr13-24909999-G-C
• rs139844197
• NM_018451.5:c.656C>G

Variant summary

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

The NM_018451.5(CENPJ):​c.656C>G​(p.Pro219Arg) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CENPJ NM_018451.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3302135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPJ	NM_018451.5	c.656C>G	p.Pro219Arg	missense_variant	Exon 4 of 17	ENST00000381884.9	NP_060921.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPJ	ENST00000381884.9	c.656C>G	p.Pro219Arg	missense_variant	Exon 4 of 17	1	NM_018451.5	ENSP00000371308.4
CENPJ	ENST00000616936.4	n.656C>G		non_coding_transcript_exon_variant	Exon 4 of 16	1		ENSP00000477511.1
CENPJ	ENST00000545981.6	n.656C>G		non_coding_transcript_exon_variant	Exon 4 of 18	2		ENSP00000441090.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.61
DEOGEN2	Benign	0.014	.;T;T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.0	.;N;N
REVEL	Benign	0.098
Sift	Uncertain	0.0050	.;D;D
Sift4G	Uncertain	0.058	T;D;T
Polyphen		0.84	.;P;.
Vest4		0.45
MutPred		0.47		Gain of catalytic residue at Y221 (P = 1e-04);Gain of catalytic residue at Y221 (P = 1e-04);Gain of catalytic residue at Y221 (P = 1e-04);
MVP		0.60
MPC		0.42
ClinPred		0.34	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.057
gMVP		0.40

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: rs139844197; hg19: chr13-25484137;