Variant 9-17135279-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017738.4(CNTLN):c.214G>A(p.Ala72Thr) 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. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CNTLN
NM_017738.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.291

Variant links:

Genes affected

CNTLN (HGNC:23432): (centlein) Enables protein domain specific binding activity; protein kinase binding activity; and protein-macromolecule adaptor activity. Involved in centriole-centriole cohesion and protein localization to organelle. Located in cytosol; microtubule organizing center; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CNTLN links:

CNTLN (HGNC:):

CNTLN links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04596901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTLN	NM_017738.4 linkuse as main transcript	c.214G>A	p.Ala72Thr	missense_variant	1/26	ENST00000380647.8	NP_060208.2	Q9NXG0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CNTLN	ENST00000380647.8 linkuse as main transcript	c.214G>A	p.Ala72Thr	missense_variant	1/26	1	NM_017738.4	ENSP00000370021.3	Q9NXG0-2
CNTLN	ENST00000380641.4 linkuse as main transcript	c.214G>A	p.Ala72Thr	missense_variant	1/7	2		ENSP00000370015.3	Q9NXG0-3
CNTLN	ENST00000484374.1 linkuse as main transcript	n.298G>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.90e-7

AC:

AN:

1448608

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718900

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2023

The c.214G>A (p.A72T) alteration is located in exon 1 (coding exon 1) of the CNTLN gene. This alteration results from a G to A substitution at nucleotide position 214, causing the alanine (A) at amino acid position 72 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

9.3

DANN

Benign

0.92

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.046

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.46

N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.29

N;N

REVEL

Benign

0.0070

Sift

Benign

0.27

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.0

B;B

Vest4

0.12

MutPred

0.13

Gain of glycosylation at A72 (P = 0.0053);Gain of glycosylation at A72 (P = 0.0053);

MVP

0.014

ClinPred

0.065

GERP RS

-0.063

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.062

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over