rs1171910750
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_012338.4(TSPAN12):c.225_227delCAT(p.Ile76del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,706 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
TSPAN12
NM_012338.4 disruptive_inframe_deletion
NM_012338.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.94
Genes affected
TSPAN12 (HGNC:21641): (tetraspanin 12) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_012338.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TSPAN12 | NM_012338.4 | c.225_227delCAT | p.Ile76del | disruptive_inframe_deletion | 4/8 | ENST00000222747.8 | NP_036470.1 | |
TSPAN12 | XM_005250239.4 | c.225_227delCAT | p.Ile76del | disruptive_inframe_deletion | 5/9 | XP_005250296.1 | ||
TSPAN12 | XM_047420095.1 | c.225_227delCAT | p.Ile76del | disruptive_inframe_deletion | 5/9 | XP_047276051.1 | ||
TSPAN12 | XM_047420096.1 | c.225_227delCAT | p.Ile76del | disruptive_inframe_deletion | 5/8 | XP_047276052.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TSPAN12 | ENST00000222747.8 | c.225_227delCAT | p.Ile76del | disruptive_inframe_deletion | 4/8 | 1 | NM_012338.4 | ENSP00000222747.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251294Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135824
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461706Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727162
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial exudative vitreoretinopathy Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
TSPAN12-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 11, 2023 | The TSPAN12 c.225_227delCAT variant is predicted to result in an in-frame deletion (p.Ile76del). This variant was reported in an individual with familial exudative vitreoretinopathy (Table S2, Patient G001414, Carss et al. 2017. PubMed ID: 28041643; Supplemental Data, Turro et al. 2020. PubMed ID: 32581362). This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-120478888-AATG-A). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
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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