chr11-99845159-T-G
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_014361.4(CNTN5):c.474T>G(p.Ile158Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00768 in 1,613,768 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0051 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0079 ( 85 hom. )
Consequence
CNTN5
NM_014361.4 missense
NM_014361.4 missense
Scores
7
11
Clinical Significance
Conservation
PhyloP100: -0.168
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.013951659).
BP6
?
Variant 11-99845159-T-G is Benign according to our data. Variant chr11-99845159-T-G is described in ClinVar as [Benign]. Clinvar id is 720168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Homozygotes in GnomAd at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNTN5 | NM_014361.4 | c.474T>G | p.Ile158Met | missense_variant | 6/25 | ENST00000524871.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTN5 | ENST00000524871.6 | c.474T>G | p.Ile158Met | missense_variant | 6/25 | 1 | NM_014361.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00514 AC: 782AN: 152074Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00539 AC: 1344AN: 249232Hom.: 13 AF XY: 0.00567 AC XY: 767AN XY: 135214
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GnomAD4 exome AF: 0.00795 AC: 11616AN: 1461576Hom.: 85 Cov.: 32 AF XY: 0.00757 AC XY: 5504AN XY: 727072
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GnomAD4 genome ? AF: 0.00514 AC: 782AN: 152192Hom.: 6 Cov.: 32 AF XY: 0.00474 AC XY: 353AN XY: 74424
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25
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
CNTN5-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 19, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;.
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;T;.
Sift4G
Uncertain
T;T;T;D;T;D
Polyphen
1.0
.;D;D;D;.;.
Vest4
MVP
MPC
0.049
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at