9-121094988-G-T

Variant names:

• chr9-121094988-G-T
• NM_007018.6:c.449G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007018.6(CNTRL):​c.449G>T​(p.Arg150Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,602 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CNTRL NM_007018.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4012461).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTRL	NM_007018.6	c.449G>T	p.Arg150Leu	missense_variant	Exon 5 of 44	ENST00000373855.7	NP_008949.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTRL	ENST00000373855.7	c.449G>T	p.Arg150Leu	missense_variant	Exon 5 of 44	5	NM_007018.6	ENSP00000362962.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455602 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 724328

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.083	T;T;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	D;.;D
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	1.4	.;L;L
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.016	D;D;D
Sift4G	Uncertain	0.019	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.61, 0.67
MutPred		0.46		Loss of MoRF binding (P = 0.1109);Loss of MoRF binding (P = 0.1109);Loss of MoRF binding (P = 0.1109);
MVP		0.57
MPC		0.23
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.45
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-123857266;