Genetic Variant FTCD:p.Thr407Met (chr21-46145457-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_206965.2(FTCD):c.1220C>T(p.Thr407Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T407K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FTCD
NM_206965.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0310

Publications

0 publications found

Variant links:

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]

FTCD Gene-Disease associations (from GenCC):

formiminoglutamic aciduria
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet, Laboratory for Molecular Medicine

FTCD links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29663944).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FTCD	NM_206965.2	MANE Select	c.1220C>T	p.Thr407Met	missense	Exon 10 of 14	NP_996848.1
FTCD	NM_001320412.2		c.1220C>T	p.Thr407Met	missense	Exon 10 of 15	NP_001307341.1
FTCD	NM_006657.3		c.1220C>T	p.Thr407Met	missense	Exon 10 of 15	NP_006648.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FTCD	ENST00000397746.8	TSL:1 MANE Select	c.1220C>T	p.Thr407Met	missense	Exon 10 of 14	ENSP00000380854.3
FTCD	ENST00000397748.5	TSL:1	c.1220C>T	p.Thr407Met	missense	Exon 10 of 15	ENSP00000380856.1
FTCD	ENST00000291670.9	TSL:1	c.1220C>T	p.Thr407Met	missense	Exon 10 of 15	ENSP00000291670.5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1408452

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

696086

African (AFR)

AF:

0.00

AC:

AN:

32002

American (AMR)

AF:

0.00

AC:

AN:

38082

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25218

East Asian (EAS)

AF:

0.00

AC:

AN:

36318

South Asian (SAS)

AF:

0.00

AC:

AN:

79916

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1085348

Other (OTH)

AF:

0.00

AC:

AN:

58360

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.37

M_CAP

Benign

0.025

MetaRNN

Benign

0.30

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

-0.031

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.57

REVEL

Benign

0.047

Sift

Benign

0.11

Sift4G

Benign

0.12

Polyphen

0.82

Vest4

0.19

MutPred

0.42

Loss of phosphorylation at T407 (P = 0.0536)

MVP

0.56

MPC

0.14

ClinPred

0.14

GERP RS

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.019

gMVP

0.10

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over