Variant 21-46138542-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FTCD	NM_206965.2 link	c.1409G>A	p.Arg470Gln	missense_variant	12/14	ENST00000397746.8	NP_996848.1	O95954-1
FTCD	NM_001320412.2 link	c.1409G>A	p.Arg470Gln	missense_variant	12/15		NP_001307341.1	O95954-2
FTCD	NM_006657.3 link	c.1409G>A	p.Arg470Gln	missense_variant	12/15		NP_006648.1	O95954-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FTCD	ENST00000397746.8 link	c.1409G>A	p.Arg470Gln	missense_variant	12/14	1	NM_206965.2	ENSP00000380854.3		O95954-1

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

GnomAD3 exomes

AF:

0.00212

AC:

424

AN:

199810

Hom.:

AF XY:

0.00217

AC XY:

240

AN XY:

110686

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 SAS exome

AF:

0.00113

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

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.000735

Gnomad4 ASJ exome

AF:

0.0278

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.00161

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000504

Gnomad4 OTH exome

AF:

0.00252

GnomAD4 genome

AF:

0.00128

AC:

195

AN:

152254

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.0282

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.00142

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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 07, 2025

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

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

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

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.019

gMVP

0.055

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

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