chr3-196052070-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001128148.3(TFRC):c.2155C>T(p.Arg719Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R719H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001128148.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TFRC | NM_001128148.3 | c.2155C>T | p.Arg719Cys | missense_variant | 19/19 | ENST00000360110.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TFRC | ENST00000360110.9 | c.2155C>T | p.Arg719Cys | missense_variant | 19/19 | 1 | NM_001128148.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152096Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251444Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135894
GnomAD4 exome AF: 0.0000520 AC: 76AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.0000550 AC XY: 40AN XY: 727242
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152096Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74298
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 21, 2022 | The c.2155C>T (p.R719C) alteration is located in exon 19 (coding exon 18) of the TFRC gene. This alteration results from a C to T substitution at nucleotide position 2155, causing the arginine (R) at amino acid position 719 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 | Nov 07, 2022 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TFRC protein function. This variant has not been reported in the literature in individuals affected with TFRC-related conditions. This variant is present in population databases (rs764730449, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 719 of the TFRC protein (p.Arg719Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at