17-7944637-C-T

Variant names:

• chr17-7944637-C-T
• rs11650083
• NM_053051.5:c.1733C>T

Variant summary

Our verdict is Likely benign. The variant received -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. 18/24 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. Synonymous variant affecting the same amino acid position (i.e. P578P) has been classified as Uncertain significance.

• 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
• Publications: 40 publications found

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]

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=0.055628985).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053051.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTROB	NM_053051.5	MANE Select	c.1733C>T	p.Pro578Leu	missense splice_region	Exon 12 of 19	NP_444279.2
	CNTROB	NM_001037144.7		c.1733C>T	p.Pro578Leu	missense splice_region	Exon 12 of 19	NP_001032221.1
	CNTROB	NM_001330124.3		c.1733C>T	p.Pro578Leu	missense splice_region	Exon 12 of 19	NP_001317053.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTROB	ENST00000563694.6	TSL:1 MANE Select	c.1733C>T	p.Pro578Leu	missense splice_region	Exon 12 of 19	ENSP00000456335.1
	CNTROB	ENST00000380262.7	TSL:1	c.1733C>T	p.Pro578Leu	missense splice_region	Exon 12 of 19	ENSP00000369614.3
	CNTROB	ENST00000961850.1		c.1733C>T	p.Pro578Leu	missense splice_region	Exon 12 of 20	ENSP00000631909.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.18
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.026
Sift	Benign	0.44	T
Sift4G	Benign	0.15	T
Polyphen		0.16	B
Vest4		0.14
MutPred		0.16		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

Other links and lift over

dbSNP: rs11650083; hg19: chr17-7847955;