21-46151701-TG-T
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_206965.2(FTCD):c.492delC(p.Ser165AlafsTer52) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
FTCD
NM_206965.2 frameshift
NM_206965.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.317
Publications
0 publications found
Genes affected
FTCD (HGNC:3974): (formimidoyltransferase cyclodeaminase) The protein encoded by this gene is a bifunctional enzyme that channels 1-carbon units from formiminoglutamate, a metabolite of the histidine degradation pathway, to the folate pool. Mutations in this gene are associated with glutamate formiminotransferase deficiency. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Dec 2009]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 21-46151701-TG-T is Pathogenic according to our data. Variant chr21-46151701-TG-T is described in ClinVar as Pathogenic. ClinVar VariationId is 3669848.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_206965.2. 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 |
|---|---|---|---|---|---|---|---|---|---|
| FTCD | NM_206965.2 | MANE Select | c.492delC | p.Ser165AlafsTer52 | frameshift | Exon 5 of 14 | NP_996848.1 | O95954-1 | |
| FTCD | NM_001320412.2 | c.492delC | p.Ser165AlafsTer52 | frameshift | Exon 5 of 15 | NP_001307341.1 | O95954-2 | ||
| FTCD | NM_006657.3 | c.492delC | p.Ser165AlafsTer52 | frameshift | Exon 5 of 15 | NP_006648.1 | O95954-1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| FTCD | ENST00000397746.8 | TSL:1 MANE Select | c.492delC | p.Ser165AlafsTer52 | frameshift | Exon 5 of 14 | ENSP00000380854.3 | O95954-1 | |
| FTCD | ENST00000397748.5 | TSL:1 | c.492delC | p.Ser165AlafsTer52 | frameshift | Exon 5 of 15 | ENSP00000380856.1 | O95954-2 | |
| FTCD | ENST00000291670.9 | TSL:1 | c.492delC | p.Ser165AlafsTer52 | frameshift | Exon 5 of 15 | ENSP00000291670.5 | O95954-1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 34 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152226
Hom.:
Cov.:
34
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: 6.85e-7 AC: 1AN: 1460638Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726614 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1460638
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
726614
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33476
American (AMR)
AF:
AC:
1
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26128
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
52278
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111948
Other (OTH)
AF:
AC:
0
AN:
60372
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74370 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
152226
Hom.:
Cov.:
34
AF XY:
AC XY:
1
AN XY:
74370
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
41464
American (AMR)
AF:
AC:
1
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5200
South Asian (SAS)
AF:
AC:
0
AN:
4836
European-Finnish (FIN)
AF:
AC:
0
AN:
10628
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68018
Other (OTH)
AF:
AC:
0
AN:
2094
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.325
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
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60-65
65-70
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>80
Age
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Glutamate formiminotransferase 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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