rs760722691
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PP3_ModerateBS2
The NM_012064.4(MIP):c.323C>T(p.Thr108Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
MIP
NM_012064.4 missense
NM_012064.4 missense
Scores
10
5
4
Clinical Significance
Conservation
PhyloP100: 9.60
Genes affected
MIP (HGNC:7103): (major intrinsic protein of lens fiber) Major intrinsic protein is a member of the water-transporting aquaporins as well as the original member of the MIP family of channel proteins. The function of the fiber cell membrane protein encoded by this gene is undetermined, yet this protein is speculated to play a role in intracellular communication. The MIP protein is expressed in the ocular lens and is required for correct lens function. This gene has been mapped among aquaporins AQP2, AQP5, and AQP6, in a potential gene cluster at 12q13. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM1
?
In a chain Lens fiber major intrinsic protein (size 262) in uniprot entity MIP_HUMAN there are 14 pathogenic changes around while only 3 benign (82%) in NM_012064.4
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.912
BS2
?
High AC in GnomAdExome4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MIP | NM_012064.4 | c.323C>T | p.Thr108Ile | missense_variant | 1/4 | ENST00000652304.1 | |
MIP | XM_011538354.2 | c.76-536C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MIP | ENST00000652304.1 | c.323C>T | p.Thr108Ile | missense_variant | 1/4 | NM_012064.4 | P1 | ||
MIP | ENST00000555551.1 | n.317-536C>T | intron_variant, non_coding_transcript_variant | 1 | |||||
MIP | ENST00000648442.1 | n.494-536C>T | intron_variant, non_coding_transcript_variant | ||||||
MIP | ENST00000650166.1 | n.250-536C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250768Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135790
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461790Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727208
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
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Cov.:
32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cataract 15 multiple types Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Benign
D
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Loss of glycosylation at T108 (P = 0.0117);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
Splicing
Name
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