9-121098471-A-G

Variant names:

• chr9-121098471-A-G
• rs150932215
• NM_007018.6:c.707A>G

Variant summary

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

The NM_007018.6(CNTRL):​c.707A>G​(p.Tyr236Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000299 in 1,613,712 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (0 hom.)
• Consequence: CNTRL NM_007018.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.10
• Publications: 4 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.

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.707A>G	p.Tyr236Cys	missense	Exon 7 of 44	NP_008949.4
	CNTRL	NM_001369893.1		c.707A>G	p.Tyr236Cys	missense	Exon 6 of 32	NP_001356822.1	Q5JVD1
	CNTRL	NM_001369894.1		c.707A>G	p.Tyr236Cys	missense	Exon 6 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.707A>G	p.Tyr236Cys	missense	Exon 7 of 44	ENSP00000362962.1	Q7Z7A1-1
	CNTRL	ENST00000373847.6	TSL:1	c.707A>G	p.Tyr236Cys	missense	Exon 6 of 32	ENSP00000362953.2	Q5JVD1
	CNTRL	ENST00000934490.1		c.707A>G	p.Tyr236Cys	missense	Exon 7 of 43	ENSP00000604549.1

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152070 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000203 AC: 51 AN: 251338 AF XY: 0.000184

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000378

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000309 AC: 451 AN: 1461524 Hom.: 0 Cov.: 31 AF XY: 0.000272 AC XY: 198 AN XY: 727064

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.000157 AC: 7 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000380 AC: 422 AN: 1111708

Other (OTH) AF: 0.000331 AC: 20 AN: 60386

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74398

African (AFR) AF: 0.0000482 AC: 2 AN: 41524

American (AMR) AF: 0.000196 AC: 3 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000327 Hom.: 0

Bravo AF: 0.000238

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000189 AC: 23

EpiCase AF: 0.000491

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.1
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.037	D
Polyphen		1.0	D
Vest4		0.58
MVP		0.64
MPC		0.36
ClinPred		0.43	T
GERP RS		4.5
Varity_R		0.26
gMVP		0.66
Mutation Taster		=33/167	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs150932215; hg19: chr9-123860749;