rs886048601
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1
The NM_006019.4(TCIRG1):c.2285_2290dup(p.Leu762_Gly763dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.00361 in 1,613,774 control chromosomes in the GnomAD database, including 196 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. I758I) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.019 ( 101 hom., cov: 33)
Exomes 𝑓: 0.0020 ( 95 hom. )
Consequence
TCIRG1
NM_006019.4 inframe_insertion
NM_006019.4 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.46
Genes affected
TCIRG1 (HGNC:11647): (T cell immune regulator 1, ATPase H+ transporting V0 subunit a3) This gene encodes a subunit of a large protein complex known as a vacuolar H+-ATPase (V-ATPase). The protein complex acts as a pump to move protons across the membrane. This movement of protons helps regulate the pH of cells and their surrounding environment. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, and receptor-mediated endocytosis. V-ATPase is comprised of a cytosolic V1 domain and a transmembrane V0 domain. Alternative splicing results in multiple transcript variants. Mutations in this gene are associated with infantile malignant osteopetrosis. [provided by RefSeq, May 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP3
?
Nonframeshift variant in repetitive region in NM_006019.4
BP6
?
Variant 11-68050524-A-AGGCCTG is Benign according to our data. Variant chr11-68050524-A-AGGCCTG is described in ClinVar as [Likely_benign]. Clinvar id is 305820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0649 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCIRG1 | NM_006019.4 | c.2285_2290dup | p.Leu762_Gly763dup | inframe_insertion | 19/20 | ENST00000265686.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCIRG1 | ENST00000265686.8 | c.2285_2290dup | p.Leu762_Gly763dup | inframe_insertion | 19/20 | 1 | NM_006019.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0194 AC: 2954AN: 152188Hom.: 101 Cov.: 33
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GnomAD3 exomes AF: 0.00509 AC: 1278AN: 251248Hom.: 34 AF XY: 0.00391 AC XY: 531AN XY: 135850
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GnomAD4 exome AF: 0.00196 AC: 2864AN: 1461468Hom.: 95 Cov.: 33 AF XY: 0.00168 AC XY: 1222AN XY: 727064
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GnomAD4 genome ? AF: 0.0194 AC: 2956AN: 152306Hom.: 101 Cov.: 33 AF XY: 0.0183 AC XY: 1364AN XY: 74468
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 26, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Osteopetrosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at