chr12-123584643-A-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_006815.4(TMED2):c.7A>T(p.Thr3Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000801 in 1,610,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 35)
Exomes 𝑓: 0.000085 ( 0 hom. )
Consequence
TMED2
NM_006815.4 missense
NM_006815.4 missense
Scores
1
2
16
Clinical Significance
Conservation
PhyloP100: 5.78
Genes affected
TMED2 (HGNC:16996): (transmembrane p24 trafficking protein 2) Involved in several processes, including Golgi organization; negative regulation of GTPase activity; and protein localization to plasma membrane. Located in Golgi apparatus; endoplasmic reticulum; and endoplasmic reticulum-Golgi intermediate compartment. [provided by Alliance of Genome Resources, Apr 2022]
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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=0.19607383).
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMED2 | NM_006815.4 | c.7A>T | p.Thr3Ser | missense_variant | 1/4 | ENST00000262225.8 | |
TMED2 | NM_001321445.2 | c.7A>T | p.Thr3Ser | missense_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMED2 | ENST00000262225.8 | c.7A>T | p.Thr3Ser | missense_variant | 1/4 | 1 | NM_006815.4 | P1 | |
TMED2-DT | ENST00000498967.3 | n.473T>A | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152144Hom.: 0 Cov.: 35
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GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248022Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134674
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GnomAD4 exome AF: 0.0000850 AC: 124AN: 1458818Hom.: 0 Cov.: 35 AF XY: 0.0000868 AC XY: 63AN XY: 725832
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152144Hom.: 0 Cov.: 35 AF XY: 0.0000135 AC XY: 1AN XY: 74326
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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 | Mar 29, 2023 | The c.7A>T (p.T3S) alteration is located in exon 1 (coding exon 1) of the TMED2 gene. This alteration results from a A to T substitution at nucleotide position 7, causing the threonine (T) at amino acid position 3 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
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Gain of disorder (P = 0.0272);Gain of disorder (P = 0.0272);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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