rs1555905454
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000381.4(MID1):c.34A>G(p.Ile12Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 22)
Consequence
MID1
NM_000381.4 missense
NM_000381.4 missense
Scores
2
5
10
Clinical Significance
Conservation
PhyloP100: 7.86
Genes affected
MID1 (HGNC:7095): (midline 1) The protein encoded by this gene is a member of the tripartite motif (TRIM) family, also known as the 'RING-B box-coiled coil' (RBCC) subgroup of RING finger proteins. 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. This protein forms homodimers which associate with microtubules in the cytoplasm. The protein is likely involved in the formation of multiprotein structures acting as anchor points to microtubules. Mutations in this gene have been associated with the X-linked form of Opitz syndrome, which is characterized by midline abnormalities such as cleft lip, laryngeal cleft, heart defects, hypospadias, and agenesis of the corpus callosum. This gene was also the first example of a gene subject to X inactivation in human while escaping it in mouse. Alternative promoter use, alternative splicing and alternative polyadenylation result in multiple transcript variants that have different tissue specificities. [provided by RefSeq, Dec 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MID1 | NM_000381.4 | c.34A>G | p.Ile12Val | missense_variant | 2/10 | ENST00000317552.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MID1 | ENST00000317552.9 | c.34A>G | p.Ile12Val | missense_variant | 2/10 | 1 | NM_000381.4 | P1 | |
ENST00000706950.1 | c.*36A>G | 3_prime_UTR_variant | 2/2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
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 | Apr 25, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T;T;.;.;T;T;T
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;.;.;.;.;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;N;N;N;N;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N;N;N;N;N;.;.;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;T;T;.;.;T
Sift4G
Benign
T;T;T;T;T;T;T;.;T;T;.
Polyphen
B;B;B;B;B;B;B;P;.;.;B
Vest4
MutPred
Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at