NM_206965.2:c.382G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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 Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0022 ( 4 hom. )

Consequence

FTCD
NM_206965.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter U:1B:2

Conservation

PhyloP100: 5.56

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 links:

FTCD-AS1 (HGNC:40243): (FTCD antisense RNA 1)

FTCD-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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 [Benign]. Clinvar id is 340437.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00149 (227/152336) while in subpopulation NFE AF= 0.00273 (186/68018). AF 95% confidence interval is 0.00241. There are 0 homozygotes in gnomad4. There are 104 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTCD	NM_206965.2 link	c.382G>A	p.Glu128Lys	missense_variant	Exon 4 of 14	ENST00000397746.8	NP_996848.1	O95954-1
FTCD	NM_001320412.2 link	c.382G>A	p.Glu128Lys	missense_variant	Exon 4 of 15		NP_001307341.1	O95954-2
FTCD	NM_006657.3 link	c.382G>A	p.Glu128Lys	missense_variant	Exon 4 of 15		NP_006648.1	O95954-1
FTCD-AS1	NR_170989.1 link	n.146+207C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTCD	ENST00000397746.8 link	c.382G>A	p.Glu128Lys	missense_variant	Exon 4 of 14	1	NM_206965.2	ENSP00000380854.3		O95954-1

Frequencies

GnomAD3 genomes

AF:

0.00148

AC:

226

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00273

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00189

AC:

322

AN:

170660

Hom.:

AF XY:

0.00212

AC XY:

196

AN XY:

92504

show subpopulations

Gnomad AFR exome

AF:

0.000112

Gnomad AMR exome

AF:

0.000226

Gnomad ASJ exome

AF:

0.000696

Gnomad EAS exome

AF:

0.000475

Gnomad SAS exome

AF:

0.000624

Gnomad FIN exome

AF:

0.00138

Gnomad NFE exome

AF:

0.00367

Gnomad OTH exome

AF:

0.00259

GnomAD4 exome

AF:

0.00222

AC:

3141

AN:

1414650

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

1529

AN XY:

699604

show subpopulations

Gnomad4 AFR exome

AF:

0.000278

Gnomad4 AMR exome

AF:

0.000369

Gnomad4 ASJ exome

AF:

0.000947

Gnomad4 EAS exome

AF:

0.000216

Gnomad4 SAS exome

AF:

0.000545

Gnomad4 FIN exome

AF:

0.00195

Gnomad4 NFE exome

AF:

0.00263

Gnomad4 OTH exome

AF:

0.00150

GnomAD4 genome

AF:

0.00149

AC:

227

AN:

152336

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

104

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00273

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00258

Hom.:

Bravo

AF:

0.00147

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00248

AC:

ExAC

AF:

0.00206

AC:

240

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual disability

Uncertain:1

Jan 01, 2019

Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Glutamate formiminotransferase deficiency

Benign:1

Dec 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

FTCD-related disorder

Benign:1

Feb 28, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.21

T;.;T;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.51

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

.;D;D;D

MetaRNN

Benign

0.017

T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.94

L;L;L;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.5

N;N;N;N

REVEL

Benign

0.21

Sift

Benign

0.31

T;T;T;T

Sift4G

Benign

0.62

T;T;T;T

Polyphen

0.11

B;B;B;B

Vest4

0.58

MVP

0.82

MPC

0.071

ClinPred

0.033

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.23

gMVP

0.82

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over