chr1-12192865-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001066.3(TNFRSF1B):āc.554G>Cā(p.Cys185Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000342 in 1,460,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_001066.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNFRSF1B | NM_001066.3 | c.554G>C | p.Cys185Ser | missense_variant, splice_region_variant | 6/10 | ENST00000376259.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNFRSF1B | ENST00000376259.7 | c.554G>C | p.Cys185Ser | missense_variant, splice_region_variant | 6/10 | 1 | NM_001066.3 | P1 | |
TNFRSF1B | ENST00000492361.1 | n.543G>C | splice_region_variant, non_coding_transcript_exon_variant | 5/9 | 1 | ||||
TNFRSF1B | ENST00000489921.1 | n.266G>C | splice_region_variant, non_coding_transcript_exon_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248328Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134314
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460780Hom.: 0 Cov.: 32 AF XY: 0.00000551 AC XY: 4AN XY: 726604
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 21, 2024 | The c.554G>C (p.C185S) alteration is located in exon 6 (coding exon 6) of the TNFRSF1B gene. This alteration results from a G to C substitution at nucleotide position 554, causing the cysteine (C) at amino acid position 185 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at