7-100641038-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_003227.4(TFR2):c.224C>T(p.Ala75Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000303 in 1,601,638 control chromosomes in the GnomAD database, including 1 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). Synonymous variant affecting the same amino acid position (i.e. A75A) has been classified as Likely benign.
Frequency
Consequence
NM_003227.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TFR2 | NM_003227.4 | c.224C>T | p.Ala75Val | missense_variant | 2/18 | ENST00000223051.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TFR2 | ENST00000223051.8 | c.224C>T | p.Ala75Val | missense_variant | 2/18 | 1 | NM_003227.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000224 AC: 34AN: 152092Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000433 AC: 104AN: 240090Hom.: 0 AF XY: 0.000415 AC XY: 54AN XY: 130130
GnomAD4 exome AF: 0.000311 AC: 451AN: 1449428Hom.: 1 Cov.: 31 AF XY: 0.000307 AC XY: 221AN XY: 719602
GnomAD4 genome AF: 0.000223 AC: 34AN: 152210Hom.: 0 Cov.: 31 AF XY: 0.000215 AC XY: 16AN XY: 74414
ClinVar
Submissions by phenotype
Hemochromatosis type 3 Uncertain:1Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Hereditary hemochromatosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at