11-99556237-T-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_014361.4(CNTN5):c.23T>A(p.Met8Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000027 in 1,518,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
CNTN5
NM_014361.4 missense
NM_014361.4 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 3.96
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 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=0.041709602).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNTN5 | NM_014361.4 | c.23T>A | p.Met8Lys | missense_variant | 3/25 | ENST00000524871.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTN5 | ENST00000524871.6 | c.23T>A | p.Met8Lys | missense_variant | 3/25 | 1 | NM_014361.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000178 AC: 27AN: 151690Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000469 AC: 7AN: 149354Hom.: 0 AF XY: 0.0000126 AC XY: 1AN XY: 79054
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GnomAD4 exome AF: 0.0000102 AC: 14AN: 1366584Hom.: 0 Cov.: 27 AF XY: 0.00000594 AC XY: 4AN XY: 673504
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GnomAD4 genome AF: 0.000178 AC: 27AN: 151690Hom.: 0 Cov.: 31 AF XY: 0.000135 AC XY: 10AN XY: 74088
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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 | Mar 18, 2024 | The c.23T>A (p.M8K) alteration is located in exon 1 (coding exon 1) of the CNTN5 gene. This alteration results from a T to A substitution at nucleotide position 23, causing the methionine (M) at amino acid position 8 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
.;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;N
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
0.0010
.;B;B;B
Vest4
MVP
MPC
0.047
ClinPred
T
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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