rs112775194
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_020070.4(IGLL1):c.437C>T(p.Thr146Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000822 in 1,457,490 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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. T146T) has been classified as Likely benign.
Frequency
Consequence
NM_020070.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGLL1 | NM_020070.4 | c.437C>T | p.Thr146Met | missense_variant | 3/3 | ENST00000330377.3 | |
IGLL1 | NM_001369906.1 | c.440C>T | p.Thr147Met | missense_variant | 3/3 | ||
IGLL1 | NM_152855.3 | c.*66C>T | 3_prime_UTR_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGLL1 | ENST00000330377.3 | c.437C>T | p.Thr146Met | missense_variant | 3/3 | 1 | NM_020070.4 | P1 | |
IGLL1 | ENST00000249053.3 | c.*66C>T | 3_prime_UTR_variant | 2/2 | 1 | ||||
ENST00000458318.2 | n.397G>A | non_coding_transcript_exon_variant | 4/4 | 3 | |||||
IGLL1 | ENST00000438703.1 | c.440C>T | p.Thr147Met | missense_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 173AN: 151764Hom.: 1 Cov.: 32 FAILED QC
GnomAD3 exomes AF: 0.00106 AC: 267AN: 251096Hom.: 1 AF XY: 0.00118 AC XY: 160AN XY: 135698
GnomAD4 exome AF: 0.000822 AC: 1198AN: 1457490Hom.: 4 Cov.: 33 AF XY: 0.000885 AC XY: 642AN XY: 725050
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00115 AC: 175AN: 151882Hom.: 1 Cov.: 32 AF XY: 0.00121 AC XY: 90AN XY: 74270
ClinVar
Submissions by phenotype
Agammaglobulinemia 2, autosomal recessive Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 02, 2023 | The IGLL1 c.437C>T, p.Thr146Met variant (rs112775194), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 547919). This variant is found in the East Asian population with an allele frequency of 0.5% (91/19,954 alleles) in the Genome Aggregation Database. The threonine at codon 146 is weakly conserved, but computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of the p.Thr146Met variant is uncertain at this time. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jan 10, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | IGLL1: BP4, BS2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at