chr12-125350040-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001366854.1(TMEM132B):c.656C>T(p.Thr219Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000409 in 1,614,092 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 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000042 ( 0 hom. )
Consequence
TMEM132B
NM_001366854.1 missense
NM_001366854.1 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 5.87
Genes affected
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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=0.057680547).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM132B | NM_001366854.1 | c.656C>T | p.Thr219Met | missense_variant | 2/9 | ENST00000682704.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM132B | ENST00000682704.1 | c.656C>T | p.Thr219Met | missense_variant | 2/9 | NM_001366854.1 | P2 | ||
TMEM132B | ENST00000299308.7 | c.641C>T | p.Thr214Met | missense_variant | 2/9 | 5 | A2 | ||
TMEM132B | ENST00000534945.2 | n.589C>T | non_coding_transcript_exon_variant | 1/4 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152214Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000762 AC: 19AN: 249446Hom.: 0 AF XY: 0.0000665 AC XY: 9AN XY: 135344
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GnomAD4 exome AF: 0.0000417 AC: 61AN: 1461878Hom.: 0 Cov.: 35 AF XY: 0.0000454 AC XY: 33AN XY: 727236
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74360
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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 | May 25, 2022 | The c.641C>T (p.T214M) alteration is located in exon 2 (coding exon 2) of the TMEM132B gene. This alteration results from a C to T substitution at nucleotide position 641, causing the threonine (T) at amino acid position 214 to be replaced by a methionine (M). 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
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
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