17-7944637-C-T

Position:

• chr17-7944637-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_053051.5(CNTROB):​c.1733C>T​(p.Pro578Leu) variant causes a missense, splice region 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. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. P578Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNTROB NM_053051.5 missense, splice_region
• Scores: Splicing: ADA: 0.001172
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178

Genes affected

CNTROB (HGNC:29616): (centrobin, centriole duplication and spindle assembly protein) This gene encodes a centrosomal protein that interacts with BRCA2, and is required for centriole duplication and cytokinesis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

CNTROB (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055628985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTROB	NM_053051.5	c.1733C>T	p.Pro578Leu	missense_variant, splice_region_variant	12/19	ENST00000563694.6	NP_444279.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTROB	ENST00000563694.6	c.1733C>T	p.Pro578Leu	missense_variant, splice_region_variant	12/19	1	NM_053051.5	ENSP00000456335.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.5
DANN	Benign	0.49
DEOGEN2	Benign	0.0083	.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.056	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L;L;L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.18	N;N;N
REVEL	Benign	0.026
Sift	Benign	0.44	T;T;T
Sift4G	Benign	0.15	T;T;T
Polyphen		0.16	B;B;B
Vest4		0.14
MutPred		0.16		Loss of glycosylation at P578 (P = 0.0029);Loss of glycosylation at P578 (P = 0.0029);Loss of glycosylation at P578 (P = 0.0029);
MVP		0.26
MPC		0.23
ClinPred		0.022	T
GERP RS		-2.4
Varity_R		0.014
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0012
dbscSNV1_RF	Benign	0.064
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: rs11650083; hg19: chr17-7847955;