rs148920158

Positions:

chr21-46145457-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_206965.2(FTCD):c.1220C>A(p.Thr407Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,560,728 control chromosomes in the GnomAD database, including 17 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 0.0011 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 16 hom. )

Consequence

FTCD
NM_206965.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0310

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012105256).

BP6

Variant 21-46145457-G-T is Benign according to our data. Variant chr21-46145457-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 340422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46145457-G-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0011 (167/152278) while in subpopulation NFE AF= 0.000985 (67/68014). AF 95% confidence interval is 0.000795. There are 1 homozygotes in gnomad4. There are 83 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FTCD	NM_206965.2 link	c.1220C>A	p.Thr407Lys	missense_variant	10/14	ENST00000397746.8	NP_996848.1	O95954-1
FTCD	NM_001320412.2 link	c.1220C>A	p.Thr407Lys	missense_variant	10/15		NP_001307341.1	O95954-2
FTCD	NM_006657.3 link	c.1220C>A	p.Thr407Lys	missense_variant	10/15		NP_006648.1	O95954-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FTCD	ENST00000397746.8 link	c.1220C>A	p.Thr407Lys	missense_variant	10/14	1	NM_206965.2	ENSP00000380854.3		O95954-1

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

167

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000985

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00200

AC:

337

AN:

168516

Hom.:

AF XY:

0.00190

AC XY:

172

AN XY:

90582

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000704

Gnomad ASJ exome

AF:

0.0235

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000212

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00141

Gnomad OTH exome

AF:

0.00351

GnomAD4 exome

AF:

0.00136

AC:

1910

AN:

1408450

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

943

AN XY:

696084

show subpopulations

Gnomad4 AFR exome

AF:

0.000187

Gnomad4 AMR exome

AF:

0.000814

Gnomad4 ASJ exome

AF:

0.0226

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000175

Gnomad4 FIN exome

AF:

0.0000631

Gnomad4 NFE exome

AF:

0.00102

Gnomad4 OTH exome

AF:

0.00264

GnomAD4 genome

AF:

0.00110

AC:

167

AN:

152278

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.0225

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000985

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00225

Hom.:

Bravo

AF:

0.00120

ESP6500AA

AF:

0.000235

AC:

ESP6500EA

AF:

0.00201

AC:

ExAC

AF:

0.000924

AC:

106

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	FTCD: BP4 -

Glutamate formiminotransferase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.57

CADD

Benign

5.1

DANN

Benign

0.41

DEOGEN2

Benign

0.044

T;.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.099

.;T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.012

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.56

N;N;N;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.13

N;N;N;N

REVEL

Benign

0.041

Sift

Benign

0.93

T;T;T;T

Sift4G

Benign

0.88

T;T;T;T

Polyphen

0.050

B;B;B;B

Vest4

0.18

MVP

0.28

MPC

0.067

ClinPred

0.014

GERP RS

0.91

Varity_R

0.031

gMVP

0.15

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