12-82895995-A-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_152588.3(TMTC2):c.832A>G(p.Thr278Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00037 in 1,613,710 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00020 ( 3 hom. )
Consequence
TMTC2
NM_152588.3 missense
NM_152588.3 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 3.67
Genes affected
TMTC2 (HGNC:25440): (transmembrane O-mannosyltransferase targeting cadherins 2) The protein encoded by this gene is an integral membrane protein localized to the endoplasmic reticulum (ER). The encoded protein contains many tetratricopeptide repeats, sequences known for being involved in protein-protein interactions. This protein binds both the calcium uptake pump SERCA2B and the carbohydrate-binding chaperone calnexin, and it appears to play a role in calcium homeostasis in the ER. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.005887836).
BP6
?
Variant 12-82895995-A-G is Benign according to our data. Variant chr12-82895995-A-G is described in ClinVar as [Benign]. Clinvar id is 707900.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMTC2 | NM_152588.3 | c.832A>G | p.Thr278Ala | missense_variant | 3/12 | ENST00000321196.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMTC2 | ENST00000321196.8 | c.832A>G | p.Thr278Ala | missense_variant | 3/12 | 1 | NM_152588.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00198 AC: 301AN: 151708Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000505 AC: 127AN: 251356Hom.: 1 AF XY: 0.000250 AC XY: 34AN XY: 135844
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GnomAD4 exome AF: 0.000201 AC: 294AN: 1461884Hom.: 3 Cov.: 31 AF XY: 0.000179 AC XY: 130AN XY: 727242
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GnomAD4 genome ? AF: 0.00200 AC: 303AN: 151826Hom.: 0 Cov.: 32 AF XY: 0.00174 AC XY: 129AN XY: 74178
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jun 21, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
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
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;B;.
Vest4
MVP
MPC
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