9-121096555-A-T

Variant names:

• chr9-121096555-A-T
• rs1472915368
• NM_007018.6:c.613A>T

Variant summary

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

The NM_007018.6(CNTRL):​c.613A>T​(p.Ile205Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000762 in 1,312,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. I205V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: CNTRL NM_007018.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.55
• 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=0.12669358).

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.613A>T	p.Ile205Leu	missense	Exon 6 of 44	NP_008949.4
	CNTRL	NM_001369893.1		c.613A>T	p.Ile205Leu	missense	Exon 5 of 32	NP_001356822.1	Q5JVD1
	CNTRL	NM_001369894.1		c.613A>T	p.Ile205Leu	missense	Exon 5 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.613A>T	p.Ile205Leu	missense	Exon 6 of 44	ENSP00000362962.1	Q7Z7A1-1
	CNTRL	ENST00000373847.6	TSL:1	c.613A>T	p.Ile205Leu	missense	Exon 5 of 32	ENSP00000362953.2	Q5JVD1
	CNTRL	ENST00000934490.1		c.613A>T	p.Ile205Leu	missense	Exon 6 of 43	ENSP00000604549.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.62e-7 AC: 1 AN: 1312532 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 644792

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29628

American (AMR) AF: 0.00 AC: 0 AN: 32346

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22116

East Asian (EAS) AF: 0.00 AC: 0 AN: 36206

South Asian (SAS) AF: 0.00 AC: 0 AN: 58230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5154

European-Non Finnish (NFE) AF: 9.73e-7 AC: 1 AN: 1028206

Other (OTH) AF: 0.00 AC: 0 AN: 53044

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.023
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.0	N
PhyloP100		3.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.084
Sift	Benign	0.59	T
Sift4G	Benign	0.38	T
Polyphen		0.046	B
Vest4		0.50
MutPred		0.63		Gain of disorder (P = 0.0759)
MVP		0.17
MPC		0.057
ClinPred		0.80	D
GERP RS		3.6
Varity_R		0.063
gMVP		0.21
Mutation Taster		=32/168	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: rs1472915368; hg19: chr9-123858833;