rs61729373
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_206965.2(FTCD):c.382G>A(p.Glu128Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00215 in 1,566,986 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0015 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0022 ( 4 hom. )
Consequence
FTCD
NM_206965.2 missense
NM_206965.2 missense
Scores
2
15
Clinical Significance
Conservation
PhyloP100: 5.56
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.017312586).
BP6
?
Variant 21-46151966-C-T is Benign according to our data. Variant chr21-46151966-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 340437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Homozygotes in GnomAdExome4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FTCD | NM_206965.2 | c.382G>A | p.Glu128Lys | missense_variant | 4/14 | ENST00000397746.8 | |
FTCD-AS1 | NR_170989.1 | n.146+207C>T | intron_variant, non_coding_transcript_variant | ||||
FTCD | NM_001320412.2 | c.382G>A | p.Glu128Lys | missense_variant | 4/15 | ||
FTCD | NM_006657.3 | c.382G>A | p.Glu128Lys | missense_variant | 4/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FTCD | ENST00000397746.8 | c.382G>A | p.Glu128Lys | missense_variant | 4/14 | 1 | NM_206965.2 | P1 | |
FTCD-AS1 | ENST00000446649.1 | n.146+207C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00148 AC: 226AN: 152218Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.00189 AC: 322AN: 170660Hom.: 0 AF XY: 0.00212 AC XY: 196AN XY: 92504
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GnomAD4 exome AF: 0.00222 AC: 3141AN: 1414650Hom.: 4 Cov.: 31 AF XY: 0.00219 AC XY: 1529AN XY: 699604
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GnomAD4 genome ? AF: 0.00149 AC: 227AN: 152336Hom.: 0 Cov.: 34 AF XY: 0.00140 AC XY: 104AN XY: 74486
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ExAC
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Intellectual disability Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille | Jan 01, 2019 | - - |
FTCD-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 28, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Glutamate formiminotransferase deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;B;B;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at