chr12-57782823-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005726.6(TSFM):c.22C>T(p.Arg8Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000201 in 1,595,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R8P) has been classified as Uncertain significance.
Frequency
Consequence
NM_005726.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSFM | NM_005726.6 | c.22C>T | p.Arg8Cys | missense_variant | 1/6 | ENST00000652027.2 | |
TSFM | NM_001172696.2 | c.22C>T | p.Arg8Cys | missense_variant | 1/7 | ||
TSFM | NM_001172697.2 | c.22C>T | p.Arg8Cys | missense_variant | 1/6 | ||
TSFM | NM_001172695.2 | c.22C>T | p.Arg8Cys | missense_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSFM | ENST00000652027.2 | c.22C>T | p.Arg8Cys | missense_variant | 1/6 | NM_005726.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000774 AC: 17AN: 219502Hom.: 0 AF XY: 0.0000337 AC XY: 4AN XY: 118662
GnomAD4 exome AF: 0.0000201 AC: 29AN: 1442944Hom.: 0 Cov.: 30 AF XY: 0.0000112 AC XY: 8AN XY: 716126
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74354
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 08, 2022 | The c.22C>T (p.R8C) alteration is located in exon 1 (coding exon 1) of the TSFM gene. This alteration results from a C to T substitution at nucleotide position 22, causing the arginine (R) at amino acid position 8 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 8 of the TSFM protein (p.Arg8Cys). This variant is present in population databases (rs755773165, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with TSFM-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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