9-121088358-C-G

Variant names:

• chr9-121088358-C-G
• rs1244530507
• NM_007018.6:c.32C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001369895.1(CNTRL):​c.-339C>G variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNTRL NM_001369895.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.979
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07990885).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369895.1. 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
	CNTRL	NM_007018.6	MANE Select	c.32C>G	p.Ser11Cys	missense	Exon 3 of 44	NP_008949.4
	CNTRL	NM_001369895.1		c.-339C>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 32	NP_001356824.1
	CNTRL	NM_001369893.1		c.32C>G	p.Ser11Cys	missense	Exon 2 of 32	NP_001356822.1	Q5JVD1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTRL	ENST00000373855.7	TSL:5 MANE Select	c.32C>G	p.Ser11Cys	missense	Exon 3 of 44	ENSP00000362962.1	Q7Z7A1-1
	CNTRL	ENST00000373847.6	TSL:1	c.32C>G	p.Ser11Cys	missense	Exon 2 of 32	ENSP00000362953.2	Q5JVD1
	CNTRL	ENST00000934490.1		c.32C>G	p.Ser11Cys	missense	Exon 3 of 43	ENSP00000604549.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.77
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.98
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.17
Sift	Benign	0.13	T
Sift4G	Benign	0.10	T
Polyphen		0.95	P
Vest4		0.075
MutPred		0.13		Loss of phosphorylation at S11 (P = 0.013)
MVP		0.16
MPC		0.18
ClinPred		0.20	T
GERP RS		3.3
Varity_R		0.067
gMVP		0.23
Mutation Taster		=89/111	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: rs1244530507; hg19: chr9-123850636;