NM_003227.4:c.1235_1237delACA
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PM4_SupportingPP5_Moderate
The NM_003227.4(TFR2):c.1235_1237delACA(p.Asn412del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000089 in 1,460,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
TFR2
NM_003227.4 disruptive_inframe_deletion
NM_003227.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.54
Publications
3 publications found
Genes affected
TFR2 (HGNC:11762): (transferrin receptor 2) This gene encodes a single-pass type II membrane protein, which is a member of the transferrin receptor-like family. This protein mediates cellular uptake of transferrin-bound iron, and may be involved in iron metabolism, hepatocyte function and erythrocyte differentiation. Mutations in this gene have been associated with hereditary hemochromatosis type III. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2011]
TFR2 Gene-Disease associations (from GenCC):
- hemochromatosis type 3Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_003227.4. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 7-100630921-ATGT-A is Pathogenic according to our data. Variant chr7-100630921-ATGT-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 21363.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_003227.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TFR2 | NM_003227.4 | MANE Select | c.1235_1237delACA | p.Asn412del | disruptive_inframe_deletion | Exon 9 of 18 | NP_003218.2 | ||
| TFR2 | NM_001206855.3 | c.722_724delACA | p.Asn241del | disruptive_inframe_deletion | Exon 6 of 15 | NP_001193784.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TFR2 | ENST00000223051.8 | TSL:1 MANE Select | c.1235_1237delACA | p.Asn412del | disruptive_inframe_deletion | Exon 9 of 18 | ENSP00000223051.3 | ||
| TFR2 | ENST00000462107.1 | TSL:5 | c.1235_1237delACA | p.Asn412del | disruptive_inframe_deletion | Exon 10 of 19 | ENSP00000420525.1 | ||
| TFR2 | ENST00000431692.5 | TSL:5 | c.978_980delACA | p.Gln326del | disruptive_inframe_deletion | Exon 7 of 16 | ENSP00000413905.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.0000199 AC: 5AN: 251196 AF XY: 0.0000295 show subpopulations
GnomAD2 exomes
AF:
AC:
5
AN:
251196
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000890 AC: 13AN: 1460866Hom.: 0 AF XY: 0.0000151 AC XY: 11AN XY: 726710 show subpopulations
GnomAD4 exome
AF:
AC:
13
AN:
1460866
Hom.:
AF XY:
AC XY:
11
AN XY:
726710
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33442
American (AMR)
AF:
AC:
0
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
9
AN:
86208
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5138
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1111822
Other (OTH)
AF:
AC:
0
AN:
60290
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.483
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hemochromatosis type 3 Pathogenic:1Other:1
Jan 28, 2024
Baylor Genetics
Significance:Likely pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing
GeneReviews
Significance:not provided
Review Status:no classification provided
Collection Method:literature only
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.