Variant 21-46136968-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000397748.5(FTCD):c.1625C>T(p.Pro542Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 1,612,796 control chromosomes in the GnomAD database, including 6,523 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.067 ( 426 hom., cov: 33)

Exomes 𝑓: 0.085 ( 6097 hom. )

Consequence

FTCD
ENST00000397748.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -3.99

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017768741).

BP6

Variant 21-46136968-G-A is Benign according to our data. Variant chr21-46136968-G-A is described in ClinVar as [Benign]. Clinvar id is 167101.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.092 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FTCD	NM_206965.2 linkuse as main transcript	c.*19C>T		3_prime_UTR_variant	14/14	ENST00000397746.8
FTCD	NM_001320412.2 linkuse as main transcript	c.1625C>T	p.Pro542Leu	missense_variant	14/15
FTCD	NM_006657.3 linkuse as main transcript	c.*2+17C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTCD	ENST00000397746.8 linkuse as main transcript	c.*19C>T		3_prime_UTR_variant	14/14	1	NM_206965.2	P1	O95954-1

Frequencies

GnomAD3 genomes

AF:

0.0668

AC:

10158

AN:

152154

Hom.:

425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0501

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0514

Gnomad ASJ

AF:

0.0884

Gnomad EAS

AF:

0.00539

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0342

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0939

Gnomad OTH

AF:

0.0655

GnomAD3 exomes

AF:

0.0598

AC:

14754

AN:

246918

Hom.:

564

AF XY:

0.0601

AC XY:

8062

AN XY:

134190

show subpopulations

Gnomad AFR exome

AF:

0.0492

Gnomad AMR exome

AF:

0.0320

Gnomad ASJ exome

AF:

0.0877

Gnomad EAS exome

AF:

0.00670

Gnomad SAS exome

AF:

0.0153

Gnomad FIN exome

AF:

0.0358

Gnomad NFE exome

AF:

0.0927

Gnomad OTH exome

AF:

0.0721

GnomAD4 exome

AF:

0.0853

AC:

124543

AN:

1460524

Hom.:

6097

Cov.:

AF XY:

0.0830

AC XY:

60329

AN XY:

726516

show subpopulations

Gnomad4 AFR exome

AF:

0.0476

Gnomad4 AMR exome

AF:

0.0345

Gnomad4 ASJ exome

AF:

0.0898

Gnomad4 EAS exome

AF:

0.00395

Gnomad4 SAS exome

AF:

0.0155

Gnomad4 FIN exome

AF:

0.0392

Gnomad4 NFE exome

AF:

0.0993

Gnomad4 OTH exome

AF:

0.0811

GnomAD4 genome

AF:

0.0668

AC:

10165

AN:

152272

Hom.:

426

Cov.:

AF XY:

0.0631

AC XY:

4701

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0502

Gnomad4 AMR

AF:

0.0514

Gnomad4 ASJ

AF:

0.0884

Gnomad4 EAS

AF:

0.00540

Gnomad4 SAS

AF:

0.0118

Gnomad4 FIN

AF:

0.0342

Gnomad4 NFE

AF:

0.0939

Gnomad4 OTH

AF:

0.0648

Alfa

AF:

0.0833

Hom.:

302

Bravo

AF:

0.0677

TwinsUK

AF:

0.107

AC:

395

ALSPAC

AF:

0.0942

AC:

363

ESP6500AA

AF:

0.0475

AC:

209

ESP6500EA

AF:

0.0949

AC:

816

ExAC

AF:

0.0609

AC:

7385

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Eurofins Ntd Llc (ga)

Mar 12, 2013

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.52

DANN

Benign

0.54

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N;N

PROVEAN

Benign

-0.23

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0010

Vest4

0.063

ClinPred

0.0014

GERP RS

-3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.29

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