chr17-5489344-A-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001258217.2(MIS12):c.482A>T(p.Glu161Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
MIS12
NM_001258217.2 missense
NM_001258217.2 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 2.73
Genes affected
MIS12 (HGNC:24967): (MIS12 kinetochore complex component) Involved in attachment of mitotic spindle microtubules to kinetochore and kinetochore assembly. Located in kinetochore and nucleus. Part of MIS12/MIND type complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.305363).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MIS12 | NM_001258217.2 | c.482A>T | p.Glu161Val | missense_variant | 3/3 | ENST00000611091.5 | NP_001245146.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MIS12 | ENST00000611091.5 | c.482A>T | p.Glu161Val | missense_variant | 3/3 | 2 | NM_001258217.2 | ENSP00000484532.1 | ||
MIS12 | ENST00000381165.3 | c.482A>T | p.Glu161Val | missense_variant | 3/3 | 1 | ENSP00000370557.3 | |||
MIS12 | ENST00000573759.1 | c.482A>T | p.Glu161Val | missense_variant | 2/2 | 1 | ENSP00000461252.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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 | Apr 08, 2024 | The c.482A>T (p.E161V) alteration is located in exon 3 (coding exon 1) of the MIS12 gene. This alteration results from a A to T substitution at nucleotide position 482, causing the glutamic acid (E) at amino acid position 161 to be replaced by a valine (V). 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;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;.;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
.;.;D
REVEL
Benign
Sift
Benign
.;.;D
Sift4G
Benign
T;T;T
Polyphen
D;D;D
Vest4
MutPred
Loss of disorder (P = 0.0621);Loss of disorder (P = 0.0621);Loss of disorder (P = 0.0621);
MVP
MPC
0.92
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
Publications
No publications associated with this variant yet.