chr1-7933162-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_001561.6(TNFRSF9):c.679C>T(p.Pro227Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000622 in 1,606,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001561.6 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNFRSF9 | NM_001561.6 | c.679C>T | p.Pro227Ser | missense_variant, splice_region_variant | 7/8 | ENST00000377507.8 | |
TNFRSF9 | XM_006710618.4 | c.679C>T | p.His227Tyr | missense_variant, splice_region_variant | 7/8 | ||
TNFRSF9 | XM_047419672.1 | c.679C>T | p.Gln227Ter | stop_gained, splice_region_variant | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNFRSF9 | ENST00000377507.8 | c.679C>T | p.Pro227Ser | missense_variant, splice_region_variant | 7/8 | 1 | NM_001561.6 | P1 | |
TNFRSF9 | ENST00000474475.1 | c.223C>T | p.His75Tyr | missense_variant, splice_region_variant | 2/3 | 3 | |||
TNFRSF9 | ENST00000492571.1 | c.*321C>T | 3_prime_UTR_variant, NMD_transcript_variant | 5/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 152054Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000150 AC: 37AN: 245962Hom.: 0 AF XY: 0.000203 AC XY: 27AN XY: 132954
GnomAD4 exome AF: 0.0000646 AC: 94AN: 1454440Hom.: 0 Cov.: 30 AF XY: 0.0000858 AC XY: 62AN XY: 722958
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74398
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 08, 2022 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 227 of the TNFRSF9 protein (p.Pro227Ser). This variant is present in population databases (rs533883433, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with TNFRSF9-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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