chr2-189571741-G-GCAA
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP3
The NM_014585.6(SLC40A1):c.487_488insTTG(p.Val162dup) variant causes a inframe insertion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
SLC40A1
NM_014585.6 inframe_insertion
NM_014585.6 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.96
Genes affected
SLC40A1 (HGNC:10909): (solute carrier family 40 member 1) The protein encoded by this gene is a cell membrane protein that may be involved in iron export from duodenal epithelial cells. Defects in this gene are a cause of hemochromatosis type 4 (HFE4). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM1
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 4 uncertain in NM_014585.6
PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_014585.6
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC40A1 | NM_014585.6 | c.487_488insTTG | p.Val162dup | inframe_insertion | 5/8 | ENST00000261024.7 | |
SLC40A1 | XM_047444066.1 | c.367_368insTTG | p.Val122dup | inframe_insertion | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC40A1 | ENST00000261024.7 | c.487_488insTTG | p.Val162dup | inframe_insertion | 5/8 | 1 | NM_014585.6 | P1 | |
SLC40A1 | ENST00000427241.5 | c.487_488insTTG | p.Val162dup | inframe_insertion | 7/8 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hemochromatosis type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 26, 2015 | In summary, this is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature. This sequence change inserts 3 nucleotides in exon 5 of the SLC40A1 mRNA (c.485_487dupTTG). This leads to the insertion of 1 amino acid residue(s) in the SLC40A1 protein (p.Val162dup) but otherwise preserves the integrity of the reading frame. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at