chr1-7920881-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001561.6(TNFRSF9):c.722G>A(p.Cys241Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000539 in 1,613,786 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001561.6 missense
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 |
---|---|---|---|---|---|---|---|---|
TNFRSF9 | NM_001561.6 | c.722G>A | p.Cys241Tyr | missense_variant | Exon 8 of 8 | ENST00000377507.8 | NP_001552.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000658 AC: 10AN: 151964Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000107 AC: 27AN: 251256Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135828
GnomAD4 exome AF: 0.0000527 AC: 77AN: 1461822Hom.: 0 Cov.: 30 AF XY: 0.0000536 AC XY: 39AN XY: 727210
GnomAD4 genome AF: 0.0000658 AC: 10AN: 151964Hom.: 0 Cov.: 31 AF XY: 0.0000674 AC XY: 5AN XY: 74226
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.722G>A (p.C241Y) alteration is located in exon 9 (coding exon 7) of the TNFRSF9 gene. This alteration results from a G to A substitution at nucleotide position 722, causing the cysteine (C) at amino acid position 241 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 241 of the TNFRSF9 protein (p.Cys241Tyr). This variant is present in population databases (rs752191416, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TNFRSF9-related conditions. ClinVar contains an entry for this variant (Variation ID: 999175). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at