11-68043010-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_006019.4(TCIRG1):c.482C>T(p.Pro161Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,551,700 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P161P) has been classified as Likely benign.
Frequency
Consequence
NM_006019.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCIRG1 | NM_006019.4 | c.482C>T | p.Pro161Leu | missense_variant | 5/20 | ENST00000265686.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCIRG1 | ENST00000265686.8 | c.482C>T | p.Pro161Leu | missense_variant | 5/20 | 1 | NM_006019.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00140 AC: 213AN: 152114Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00142 AC: 221AN: 155316Hom.: 0 AF XY: 0.00130 AC XY: 108AN XY: 82844
GnomAD4 exome AF: 0.00257 AC: 3596AN: 1399468Hom.: 7 Cov.: 35 AF XY: 0.00249 AC XY: 1718AN XY: 690538
GnomAD4 genome AF: 0.00140 AC: 213AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.00128 AC XY: 95AN XY: 74434
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:4
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 08, 2019 | Reported (as rs34227834) in association reduced neutrophil count (Rosenthal et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27229898) - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 15, 2015 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Autosomal recessive osteopetrosis 1 Benign:2
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at