NM_000281.4:c.*404_*405delGT
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_000281.4(PCBD1):c.*404_*405delGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,106,430 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
PCBD1
NM_000281.4 3_prime_UTR
NM_000281.4 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.85
Publications
0 publications found
Genes affected
PCBD1 (HGNC:8646): (pterin-4 alpha-carbinolamine dehydratase 1) This gene encodes a member of the pterin-4-alpha-carbinolamine dehydratase family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. The encoded protein functions as both a dehydratase involved in tetrahydrobiopterin biosynthesis, and as a cofactor for HNF1A-dependent transcription. A deficiency of this enzyme leads to hyperphenylalaninemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
SGPL1 (HGNC:10817): (sphingosine-1-phosphate lyase 1) Enables sphinganine-1-phosphate aldolase activity. Involved in apoptotic signaling pathway; fatty acid metabolic process; and sphingolipid metabolic process. Located in endoplasmic reticulum. Implicated in nephrotic syndrome type 14. [provided by Alliance of Genome Resources, Apr 2022]
SGPL1 Gene-Disease associations (from GenCC):
- nephrotic syndrome 14Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
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_000281.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| PCBD1 | NM_000281.4 | MANE Select | c.*404_*405delGT | 3_prime_UTR | Exon 4 of 4 | NP_000272.1 | P61457 | ||
| PCBD1 | NM_001289797.2 | c.*404_*405delGT | 3_prime_UTR | Exon 4 of 4 | NP_001276726.1 | ||||
| PCBD1 | NM_001323004.2 | c.217-1061_217-1060delGT | intron | N/A | NP_001309933.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PCBD1 | ENST00000299299.4 | TSL:1 MANE Select | c.*404_*405delGT | 3_prime_UTR | Exon 4 of 4 | ENSP00000299299.3 | P61457 | ||
| PCBD1 | ENST00000875522.1 | c.*404_*405delGT | 3_prime_UTR | Exon 4 of 4 | ENSP00000545581.1 | ||||
| PCBD1 | ENST00000875521.1 | c.*404_*405delGT | 3_prime_UTR | Exon 4 of 4 | ENSP00000545580.1 |
Frequencies
GnomAD3 genomes 0.0000197 AC: 3AN: 152216Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
3
AN:
152216
Hom.:
Cov.:
32
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: 0.0000126 AC: 12AN: 954096Hom.: 0 AF XY: 0.0000134 AC XY: 6AN XY: 448042 show subpopulations
GnomAD4 exome
AF:
AC:
12
AN:
954096
Hom.:
AF XY:
AC XY:
6
AN XY:
448042
show subpopulations
African (AFR)
AF:
AC:
1
AN:
20244
American (AMR)
AF:
AC:
0
AN:
6750
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
8176
East Asian (EAS)
AF:
AC:
0
AN:
10220
South Asian (SAS)
AF:
AC:
1
AN:
35042
European-Finnish (FIN)
AF:
AC:
0
AN:
5730
Middle Eastern (MID)
AF:
AC:
0
AN:
2088
European-Non Finnish (NFE)
AF:
AC:
9
AN:
832304
Other (OTH)
AF:
AC:
1
AN:
33542
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.408
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
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>80
Age
GnomAD4 genome 0.0000197 AC: 3AN: 152334Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74496 show subpopulations
GnomAD4 genome
AF:
AC:
3
AN:
152334
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74496
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41576
American (AMR)
AF:
AC:
0
AN:
15306
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5176
South Asian (SAS)
AF:
AC:
2
AN:
4830
European-Finnish (FIN)
AF:
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68034
Other (OTH)
AF:
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome 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
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Hyperphenylalaninemia due to tetrahydrobiopterin deficiency (1)
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
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