Variant chr11-99916074-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014361.4(CNTN5):c.598C>T(p.Arg200Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000111 in 1,611,798 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

CNTN5
NM_014361.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.49

Variant links:

Genes affected

CNTN5 (HGNC:2175): (contactin 5) The protein encoded by this gene is a member of the immunoglobulin superfamily, and contactin family, which mediate cell surface interactions during nervous system development. This protein is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein that functions as a cell adhesion molecule. It may play a role in the formation of axon connections in the developing nervous system. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

CNTN5 links:

CNTN5 (HGNC:):

CNTN5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN5	NM_014361.4 linkuse as main transcript	c.598C>T	p.Arg200Trp	missense_variant	7/25	ENST00000524871.6	NP_055176.1	O94779-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN5	ENST00000524871.6 linkuse as main transcript	c.598C>T	p.Arg200Trp	missense_variant	7/25	1	NM_014361.4	ENSP00000435637.1		O94779-1

Frequencies

GnomAD3 genomes

AF:

0.0000790

AC:

AN:

151954

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000769

AC:

AN:

247062

Hom.:

AF XY:

0.0000746

AC XY:

AN XY:

134032

show subpopulations

Gnomad AFR exome

AF:

0.0000651

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000562

Gnomad SAS exome

AF:

0.0000991

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000114

AC:

167

AN:

1459724

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

726088

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000137

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152074

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000774

Hom.:

Bravo

AF:

0.0000567

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.000116

AC:

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

Nov 21, 2024

The c.598C>T (p.R200W) alteration is located in exon 1 (coding exon 1) of the CNTN5 gene. This alteration results from a C to T substitution at nucleotide position 598, causing the arginine (R) at amino acid position 200 to be replaced by a tryptophan (W). 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

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Uncertain

0.095

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.66

.;D;D;.;T;.

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

D;.;D;D;D;D

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.60

D;D;D;D;D;D

MetaSVM

Benign

-0.58

MutationAssessor

Benign

0.97

L;L;L;.;.;.

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.6

D;D;D;D;.;.

REVEL

Uncertain

0.38

Sift

Uncertain

0.0010

D;D;D;D;.;.

Sift4G

Uncertain

0.0060

D;D;D;D;D;D

Polyphen

1.0, 1.0

.;D;D;D;.;.

Vest4

0.64

MVP

0.82

MPC

0.22

ClinPred

0.78

GERP RS

6.0

Varity_R

0.42

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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