chr11-78658368-T-C
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2
The NM_001098816.3(TENM4):āc.8000A>Gā(p.Gln2667Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000691 in 1,614,024 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0037 ( 2 hom., cov: 33)
Exomes š: 0.00038 ( 4 hom. )
Consequence
TENM4
NM_001098816.3 missense
NM_001098816.3 missense
Scores
9
9
Clinical Significance
Conservation
PhyloP100: 5.00
Genes affected
TENM4 (HGNC:29945): (teneurin transmembrane protein 4) The protein encoded by this gene plays a role in establishing proper neuronal connectivity during development. Defects in this gene have been associated with hereditary essential tremor-5. [provided by RefSeq, Oct 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TENM4. . Gene score misZ 2.7323 (greater than the threshold 3.09). Trascript score misZ 3.5261 (greater than threshold 3.09). GenCC has associacion of gene with tremor, hereditary essential, 5.
BP4
Computational evidence support a benign effect (MetaRNN=0.0096925795).
BP6
Variant 11-78658368-T-C is Benign according to our data. Variant chr11-78658368-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 786205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 562 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TENM4 | NM_001098816.3 | c.8000A>G | p.Gln2667Arg | missense_variant | 34/34 | ENST00000278550.12 | NP_001092286.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TENM4 | ENST00000278550.12 | c.8000A>G | p.Gln2667Arg | missense_variant | 34/34 | 5 | NM_001098816.3 | ENSP00000278550 | P1 | |
TENM4 | ENST00000530738.1 | c.2801-314A>G | intron_variant | 2 | ENSP00000431711 |
Frequencies
GnomAD3 genomes AF: 0.00369 AC: 562AN: 152246Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.00102 AC: 255AN: 249024Hom.: 2 AF XY: 0.000814 AC XY: 110AN XY: 135104
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GnomAD4 exome AF: 0.000378 AC: 553AN: 1461660Hom.: 4 Cov.: 31 AF XY: 0.000326 AC XY: 237AN XY: 727112
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GnomAD4 genome AF: 0.00369 AC: 562AN: 152364Hom.: 2 Cov.: 33 AF XY: 0.00380 AC XY: 283AN XY: 74508
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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 | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2024 | TENM4: BS1 - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 31, 2019 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
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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