NM_206965.2:c.1409G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_206965.2(FTCD):c.1409G>A(p.Arg470Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,586,500 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R470W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0013 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 10 hom. )

Consequence

FTCD
NM_206965.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.54

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057617426).

BP6

Variant 21-46138542-C-T is Benign according to our data. Variant chr21-46138542-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 340416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00128 (195/152254) while in subpopulation AMR AF = 0.00118 (18/15308). AF 95% confidence interval is 0.00076. There are 4 homozygotes in GnomAd4. There are 85 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
FTCD	NM_206965.2 link	c.1409G>A	p.Arg470Gln	missense_variant	Exon 12 of 14	ENST00000397746.8	NP_996848.1
FTCD	NM_001320412.2 link	c.1409G>A	p.Arg470Gln	missense_variant	Exon 12 of 15		NP_001307341.1
FTCD	NM_006657.3 link	c.1409G>A	p.Arg470Gln	missense_variant	Exon 12 of 15		NP_006648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTCD	ENST00000397746.8 link	c.1409G>A	p.Arg470Gln	missense_variant	Exon 12 of 14	1	NM_206965.2	ENSP00000380854.3

Frequencies

GnomAD3 genomes

AF:

0.00128

AC:

194

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00212

AC:

424

AN:

199810

AF XY:

0.00217

show subpopulations

Gnomad AFR exome

AF:

0.000264

Gnomad AMR exome

AF:

0.000711

Gnomad ASJ exome

AF:

0.0293

Gnomad EAS exome

AF:

0.0000629

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00101

Gnomad OTH exome

AF:

0.00270

GnomAD4 exome

AF:

0.00112

AC:

1613

AN:

1434246

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

852

AN XY:

712524

show subpopulations

African (AFR)

AF:

0.000210

AC:

AN:

33276

American (AMR)

AF:

0.000735

AC:

AN:

42202

Ashkenazi Jewish (ASJ)

AF:

0.0278

AC:

713

AN:

25674

East Asian (EAS)

AF:

0.000102

AC:

AN:

39088

South Asian (SAS)

AF:

0.00161

AC:

135

AN:

83724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40432

Middle Eastern (MID)

AF:

0.00327

AC:

AN:

4898

European-Non Finnish (NFE)

AF:

0.000504

AC:

557

AN:

1105400

Other (OTH)

AF:

0.00252

AC:

150

AN:

59552

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

101

201

302

402

503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00128

AC:

195

AN:

152254

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41552

American (AMR)

AF:

0.00118

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0282

AC:

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5164

South Asian (SAS)

AF:

0.00104

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000882

AC:

AN:

67992

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00287

Hom.:

Bravo

AF:

0.00130

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000835

AC:

ExAC

AF:

0.00133

AC:

158

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glutamate formiminotransferase deficiency

Benign:1

Jan 07, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FTCD: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.5

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.049

T;.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.23

.;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.0058

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.21

N;N;N

PhyloP100

-1.5

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.090

N;N;N

REVEL

Benign

0.015

Sift

Benign

0.41

T;T;T

Sift4G

Benign

0.59

T;T;T

Polyphen

0.0040

B;B;B

Vest4

0.095

MVP

0.12

MPC

0.064

ClinPred

0.00049

GERP RS

-1.6

PromoterAI

0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.019

gMVP

0.055

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over