rs186615197
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_014361.4(CNTN5):c.1047A>T(p.Lys349Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,613,660 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0015 ( 3 hom., cov: 33)
Exomes 𝑓: 0.0010 ( 14 hom. )
Consequence
CNTN5
NM_014361.4 missense
NM_014361.4 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 0.661
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.009718627).
BP6
Variant 11-100061278-A-T is Benign according to our data. Variant chr11-100061278-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 446039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00104 (1523/1461362) while in subpopulation AMR AF= 0.0178 (798/44716). AF 95% confidence interval is 0.0168. There are 14 homozygotes in gnomad4_exome. There are 698 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CNTN5 | NM_014361.4 | c.1047A>T | p.Lys349Asn | missense_variant | 10/25 | ENST00000524871.6 | NP_055176.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CNTN5 | ENST00000524871.6 | c.1047A>T | p.Lys349Asn | missense_variant | 10/25 | 1 | NM_014361.4 | ENSP00000435637.1 |
Frequencies
GnomAD3 genomes AF: 0.00150 AC: 229AN: 152180Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.00393 AC: 978AN: 248988Hom.: 14 AF XY: 0.00319 AC XY: 431AN XY: 135056
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GnomAD4 exome AF: 0.00104 AC: 1523AN: 1461362Hom.: 14 Cov.: 31 AF XY: 0.000960 AC XY: 698AN XY: 726968
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GnomAD4 genome AF: 0.00150 AC: 229AN: 152298Hom.: 3 Cov.: 33 AF XY: 0.00153 AC XY: 114AN XY: 74476
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 20, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 31, 2019 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T;T;T;T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;.;.
REVEL
Uncertain
Sift
Benign
T;T;T;T;.;.
Sift4G
Benign
T;T;T;T;T;T
Polyphen
1.0
.;D;D;D;.;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0531);Loss of MoRF binding (P = 0.0531);Loss of MoRF binding (P = 0.0531);.;.;.;
MVP
MPC
0.28
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