dbSNP rs376813167: CNTRL:p.Glu61Ala (chr9-121088508-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007018.6(CNTRL):c.182A>C(p.Glu61Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,084 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. E61G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CNTRL
NM_007018.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.60

Publications

0 publications found

Variant links:

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]

CNTRL links:

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ACMG classification

Classification was made for transcript

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=0.12537262).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNTRL	NM_007018.6	MANE Select	c.182A>C	p.Glu61Ala	missense	Exon 3 of 44	NP_008949.4
CNTRL	NM_001369893.1		c.182A>C	p.Glu61Ala	missense	Exon 2 of 32	NP_001356822.1	Q5JVD1
CNTRL	NM_001369894.1		c.182A>C	p.Glu61Ala	missense	Exon 2 of 30	NP_001356823.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNTRL	ENST00000373855.7	TSL:5 MANE Select	c.182A>C	p.Glu61Ala	missense	Exon 3 of 44	ENSP00000362962.1	Q7Z7A1-1
CNTRL	ENST00000373847.6	TSL:1	c.182A>C	p.Glu61Ala	missense	Exon 2 of 32	ENSP00000362953.2	Q5JVD1
CNTRL	ENST00000934490.1		c.182A>C	p.Glu61Ala	missense	Exon 3 of 43	ENSP00000604549.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459084

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726064

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33432

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109538

Other (OTH)

AF:

0.00

AC:

AN:

60292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.010

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.79

M_CAP

Benign

0.0066

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

3.6

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.79

REVEL

Benign

0.089

Sift

Uncertain

0.015

Sift4G

Uncertain

0.027

Polyphen

0.10

Vest4

0.35

MutPred

0.51

Loss of sheet (P = 0.0181)

MVP

0.38

MPC

0.066

ClinPred

0.32

GERP RS

5.0

Varity_R

0.078

gMVP

0.40

Mutation Taster

=74/126

disease causing

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over