rs184812195
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_003227.4(TFR2):c.1097G>A(p.Arg366His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000494 in 1,612,312 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R366C) has been classified as Uncertain significance.
Frequency
Consequence
NM_003227.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TFR2 | NM_003227.4 | c.1097G>A | p.Arg366His | missense_variant | 8/18 | ENST00000223051.8 | |
LOC124901709 | XR_007060454.1 | n.503+590C>T | intron_variant, non_coding_transcript_variant | ||||
TFR2 | NM_001206855.3 | c.584G>A | p.Arg195His | missense_variant | 5/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TFR2 | ENST00000223051.8 | c.1097G>A | p.Arg366His | missense_variant | 8/18 | 1 | NM_003227.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000783 AC: 119AN: 151912Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.000867 AC: 217AN: 250160Hom.: 3 AF XY: 0.000755 AC XY: 102AN XY: 135130
GnomAD4 exome AF: 0.000464 AC: 678AN: 1460282Hom.: 7 Cov.: 31 AF XY: 0.000479 AC XY: 348AN XY: 726186
GnomAD4 genome ? AF: 0.000783 AC: 119AN: 152030Hom.: 0 Cov.: 30 AF XY: 0.00102 AC XY: 76AN XY: 74308
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Jul 31, 2024 | - - |
Hemochromatosis type 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Hereditary hemochromatosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at