NM_021175.4:c.52_54dupCTC
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_021175.4(HAMP):c.52_54dupCTC(p.Leu18dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,354 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
HAMP
NM_021175.4 conservative_inframe_insertion
NM_021175.4 conservative_inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.00400
Publications
0 publications found
Genes affected
HAMP (HGNC:15598): (hepcidin antimicrobial peptide) The product encoded by this gene is involved in the maintenance of iron homeostasis, and it is necessary for the regulation of iron storage in macrophages, and for intestinal iron absorption. The preproprotein is post-translationally cleaved into mature peptides of 20, 22 and 25 amino acids, and these active peptides are rich in cysteines, which form intramolecular bonds that stabilize their beta-sheet structures. These peptides exhibit antimicrobial activity against bacteria and fungi. Mutations in this gene cause hemochromatosis type 2B, also known as juvenile hemochromatosis, a disease caused by severe iron overload that results in cardiomyopathy, cirrhosis, and endocrine failure. [provided by RefSeq, Oct 2014]
HAMP Gene-Disease associations (from GenCC):
- hemochromatosis type 2BInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
- hemochromatosis type 2Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_021175.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HAMP | NM_021175.4 | MANE Select | c.52_54dupCTC | p.Leu18dup | conservative_inframe_insertion | Exon 1 of 3 | NP_066998.1 | P81172 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HAMP | ENST00000222304.5 | TSL:1 MANE Select | c.52_54dupCTC | p.Leu18dup | conservative_inframe_insertion | Exon 1 of 3 | ENSP00000222304.2 | P81172 | |
| HAMP | ENST00000598398.5 | TSL:2 | c.52_54dupCTC | p.Leu18dup | conservative_inframe_insertion | Exon 2 of 4 | ENSP00000471894.1 | P81172 | |
| HAMP | ENST00000869749.1 | c.52_54dupCTC | p.Leu18dup | conservative_inframe_insertion | Exon 1 of 3 | ENSP00000539808.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000400 AC: 1AN: 250246 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
250246
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: 0.00000821 AC: 12AN: 1461354Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4AN XY: 726990 show subpopulations
GnomAD4 exome
AF:
AC:
12
AN:
1461354
Hom.:
Cov.:
30
AF XY:
AC XY:
4
AN XY:
726990
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33472
American (AMR)
AF:
AC:
2
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
1
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86250
European-Finnish (FIN)
AF:
AC:
0
AN:
53366
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
8
AN:
1111562
Other (OTH)
AF:
AC:
1
AN:
60382
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.467
Heterozygous variant carriers
0
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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