10-70597843-TAAAAA-T
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_001083116.3(PRF1):c.*205_*209delTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 457,546 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: 𝑓 0.0 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000011 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PRF1
NM_001083116.3 3_prime_UTR
NM_001083116.3 3_prime_UTR
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.881
Publications
0 publications found
Genes affected
PRF1 (HGNC:9360): (perforin 1) This gene encodes a protein with structural similarities to complement component C9 that is important in immunity. This protein forms membrane pores that allow the release of granzymes and subsequent cytolysis of target cells. Whether pore formation occurs in the plasma membrane of target cells or in an endosomal membrane inside target cells is subject to debate. Mutations in this gene are associated with a variety of human disease including diabetes, multiple sclerosis, lymphomas, autoimmune lymphoproliferative syndrome (ALPS), aplastic anemia, and familial hemophagocytic lymphohistiocytosis type 2 (FHL2), a rare and lethal autosomal recessive disorder of early childhood. [provided by RefSeq, Aug 2017]
PALD1 (HGNC:23530): (phosphatase domain containing paladin 1) Predicted to enable protein tyrosine phosphatase activity. Predicted to be involved in peptidyl-tyrosine dephosphorylation. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
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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_001083116.3. 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 |
|---|---|---|---|---|---|---|---|---|---|
| PRF1 | NM_001083116.3 | MANE Select | c.*205_*209delTTTTT | 3_prime_UTR | Exon 3 of 3 | NP_001076585.1 | P14222 | ||
| PRF1 | NM_005041.6 | c.*205_*209delTTTTT | 3_prime_UTR | Exon 3 of 3 | NP_005032.2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PRF1 | ENST00000441259.2 | TSL:5 MANE Select | c.*205_*209delTTTTT | 3_prime_UTR | Exon 3 of 3 | ENSP00000398568.1 | P14222 | ||
| PRF1 | ENST00000373209.2 | TSL:1 | c.*205_*209delTTTTT | 3_prime_UTR | Exon 3 of 3 | ENSP00000362305.1 | P14222 | ||
| PRF1 | ENST00000862973.1 | c.*205_*209delTTTTT | 3_prime_UTR | Exon 2 of 2 | ENSP00000533032.1 |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 139114Hom.: 0 Cov.: 0
GnomAD3 genomes
AF:
AC:
0
AN:
139114
Hom.:
Cov.:
0
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000109 AC: 5AN: 457546Hom.: 0 AF XY: 0.0000125 AC XY: 3AN XY: 240080 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
5
AN:
457546
Hom.:
AF XY:
AC XY:
3
AN XY:
240080
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
12416
American (AMR)
AF:
AC:
0
AN:
18600
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
13746
East Asian (EAS)
AF:
AC:
0
AN:
31202
South Asian (SAS)
AF:
AC:
0
AN:
43660
European-Finnish (FIN)
AF:
AC:
0
AN:
29066
Middle Eastern (MID)
AF:
AC:
0
AN:
1984
European-Non Finnish (NFE)
AF:
AC:
4
AN:
280720
Other (OTH)
AF:
AC:
1
AN:
26152
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.245
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
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10
<30
30-35
35-40
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Age
GnomAD4 genome 0.00 AC: 0AN: 139114Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 67052
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
139114
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
67052
African (AFR)
AF:
AC:
0
AN:
38046
American (AMR)
AF:
AC:
0
AN:
13652
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3270
East Asian (EAS)
AF:
AC:
0
AN:
4662
South Asian (SAS)
AF:
AC:
0
AN:
4350
European-Finnish (FIN)
AF:
AC:
0
AN:
8226
Middle Eastern (MID)
AF:
AC:
0
AN:
298
European-Non Finnish (NFE)
AF:
AC:
0
AN:
63854
Other (OTH)
AF:
AC:
0
AN:
1912
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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