9-121088492-G-C

Variant names:

• chr9-121088492-G-C
• rs10818503
• NM_007018.6:c.166G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007018.6(CNTRL):​c.166G>C​(p.Val56Leu) 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. 16/22 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: 31)
• Consequence: CNTRL NM_007018.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.847
• Publications: 43 publications found

Genes affected

CNTRL (HGNC:1858): (centriolin) This gene encodes a centrosomal protein required for the centrosome to function as a microtubule organizing center. The gene product is also associated with centrosome maturation. One version of stem cell myeloproliferative disorder is the result of a reciprocal translocation between chromosomes 8 and 9, with the breakpoint associated with fibroblast growth factor receptor 1 and centrosomal protein 1. [provided by RefSeq, Jul 2008]

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=0.055065572).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTRL	NM_007018.6	c.166G>C	p.Val56Leu	missense_variant	Exon 3 of 44	ENST00000373855.7	NP_008949.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTRL	ENST00000373855.7	c.166G>C	p.Val56Leu	missense_variant	Exon 3 of 44	5	NM_007018.6	ENSP00000362962.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.013	T;T;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.59	T;.;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.055	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	.;L;L
PhyloP100		0.85
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.22	N;N;N
REVEL	Benign	0.038
Sift	Benign	0.24	T;T;T
Sift4G	Benign	0.63	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.071, 0.077
MutPred		0.30		Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP		0.13
MPC		0.048
ClinPred		0.054	T
GERP RS		2.6
Varity_R		0.053
gMVP		0.17
Mutation Taster		=86/114	disease causing

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

Other links and lift over

dbSNP: rs10818503; hg19: chr9-123850770;