rs372623233

Variant names:

• chr9-121107844-T-A
• rs372623233
• NM_007018.6:c.851T>A

Your query was ambiguous. Multiple possible variants found:

• chr9-121107844-T-A
• chr9-121107844-T-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.851T>A​(p.Ile284Lys) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I284T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNTRL NM_007018.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.730
• 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: 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=0.026302457).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007018.6. 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.851T>A	p.Ile284Lys	missense	Exon 8 of 44	NP_008949.4
	CNTRL	NM_001369893.1		c.851T>A	p.Ile284Lys	missense	Exon 7 of 32	NP_001356822.1	Q5JVD1
	CNTRL	NM_001369894.1		c.851T>A	p.Ile284Lys	missense	Exon 7 of 30	NP_001356823.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTRL	ENST00000373855.7	TSL:5 MANE Select	c.851T>A	p.Ile284Lys	missense	Exon 8 of 44	ENSP00000362962.1	Q7Z7A1-1
	CNTRL	ENST00000373847.6	TSL:1	c.851T>A	p.Ile284Lys	missense	Exon 7 of 32	ENSP00000362953.2	Q5JVD1
	CNTRL	ENST00000934490.1		c.851T>A	p.Ile284Lys	missense	Exon 8 of 43	ENSP00000604549.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.2
DANN	Benign	0.75
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.90	N
PhyloP100		0.73
PrimateAI	Benign	0.37	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.10
Sift	Benign	0.35	T
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.26
MutPred		0.39		Loss of helix (P = 0.0093)
MVP		0.040
MPC		0.076
ClinPred		0.053	T
GERP RS		1.1
Varity_R		0.057
gMVP		0.33
Mutation Taster		=58/142	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs372623233; hg19: chr9-123870122;