5-168047448-A-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_001395460.1(TENM2):c.1208A>G(p.Asn403Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000902 in 1,551,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000057 ( 0 hom. )
Consequence
TENM2
NM_001395460.1 missense
NM_001395460.1 missense
Scores
10
9
Clinical Significance
Conservation
PhyloP100: 5.93
Genes affected
TENM2 (HGNC:29943): (teneurin transmembrane protein 2) Enables cell adhesion molecule binding activity and signaling receptor binding activity. Involved in several processes, including calcium-mediated signaling using intracellular calcium source; heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; and retrograde trans-synaptic signaling by trans-synaptic protein complex. Located in cell-cell junction and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, TENM2
BP4
?
Computational evidence support a benign effect (MetaRNN=0.38011196).
BS2
?
High AC in GnomAd at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TENM2 | NM_001395460.1 | c.1208A>G | p.Asn403Ser | missense_variant | 8/31 | ENST00000518659.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TENM2 | ENST00000518659.6 | c.1208A>G | p.Asn403Ser | missense_variant | 8/31 | 5 | NM_001395460.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152206Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000639 AC: 1AN: 156540Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 82960
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GnomAD4 exome AF: 0.00000572 AC: 8AN: 1399404Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 2AN XY: 690206
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74364
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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 | Jul 20, 2022 | The c.1208A>G (p.N403S) alteration is located in exon 6 (coding exon 6) of the TENM2 gene. This alteration results from a A to G substitution at nucleotide position 1208, causing the asparagine (N) at amino acid position 403 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Uncertain
T;T
Polyphen
P;P
Vest4
MutPred
Loss of helix (P = 0.0444);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
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