rs200061253
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_012216.4(MID2):c.758G>A(p.Arg253His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000419 in 1,096,961 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 0.000042 ( 0 hom. 10 hem. )
Consequence
MID2
NM_012216.4 missense
NM_012216.4 missense
Scores
2
4
11
Clinical Significance
Conservation
PhyloP100: 7.81
Genes affected
MID2 (HGNC:7096): (midline 2) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to microtubular structures in the cytoplasm. Alternate splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Feb 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.27916482).
BS2
?
High Hemizygotes in GnomAdExome4 at 10 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MID2 | NM_012216.4 | c.758G>A | p.Arg253His | missense_variant | 3/10 | ENST00000262843.11 | |
MID2 | NM_001382751.1 | c.698G>A | p.Arg233His | missense_variant | 3/10 | ||
MID2 | NM_052817.3 | c.758G>A | p.Arg253His | missense_variant | 3/10 | ||
MID2 | NM_001382752.1 | c.698G>A | p.Arg233His | missense_variant | 3/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MID2 | ENST00000262843.11 | c.758G>A | p.Arg253His | missense_variant | 3/10 | 1 | NM_012216.4 | ||
MID2 | ENST00000443968.2 | c.758G>A | p.Arg253His | missense_variant | 3/10 | 1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD3 exomes AF: 0.0000383 AC: 7AN: 183006Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67512
GnomAD3 exomes
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GnomAD4 exome AF: 0.0000419 AC: 46AN: 1096961Hom.: 0 Cov.: 28 AF XY: 0.0000276 AC XY: 10AN XY: 362365
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GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
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23
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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 | Genetic Services Laboratory, University of Chicago | Nov 11, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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