chr12-68155423-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000619.3(IFNG):c.431C>A(p.Ser144*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,012 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
Consequence
NM_000619.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IFNG | NM_000619.3 | c.431C>A | p.Ser144* | stop_gained | Exon 4 of 4 | ENST00000229135.4 | NP_000610.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460012Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726368
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Aplastic anemia Uncertain:1
The IFNG c.431C>A (p.Ser144Ter) variant is a stop-gained variant that is predicted to result in premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. The p.Ser144Ter variant is reported at a frequency of 0.00002 in the European (non-Finnish) population of the Exome Aggregation Consortium, but this frequency is based on only one allele in a region of good sequencing coverage. The variant is thus presumed to be rare. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for aplastic anemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at