Variant 9-17135181-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017738.4(CNTLN):c.116C>T(p.Ser39Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,610,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CNTLN
NM_017738.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.094355494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTLN	NM_017738.4 linkuse as main transcript	c.116C>T	p.Ser39Leu	missense_variant	1/26	ENST00000380647.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTLN	ENST00000380647.8 linkuse as main transcript	c.116C>T	p.Ser39Leu	missense_variant	1/26	1	NM_017738.4	P1	Q9NXG0-2
CNTLN	ENST00000380641.4 linkuse as main transcript	c.116C>T	p.Ser39Leu	missense_variant	1/7	2			Q9NXG0-3
CNTLN	ENST00000484374.1 linkuse as main transcript	n.200C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724920

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Feb 05, 2024

The c.116C>T (p.S39L) alteration is located in exon 1 (coding exon 1) of the CNTLN gene. This alteration results from a C to T substitution at nucleotide position 116, causing the serine (S) at amino acid position 39 to be replaced by a leucine (L). 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

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.094

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L

MutationTaster

Benign

0.98

N;N;N;N

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.010

Sift

Benign

0.11

T;T

Sift4G

Uncertain

0.034

D;D

Polyphen

0.0070

B;B

Vest4

0.28

MutPred

0.21

Loss of glycosylation at S39 (P = 0.0028);Loss of glycosylation at S39 (P = 0.0028);

MVP

0.076

ClinPred

0.65

GERP RS

3.5

gMVP

0.11

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

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