NM_206965.2:c.470A>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_206965.2(FTCD):c.470A>T(p.Asp157Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000676 in 1,612,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D157N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

FTCD
NM_206965.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.09

Publications

0 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 links:

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

FTCD-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06037402).

BP6

Variant 21-46151724-T-A is Benign according to our data. Variant chr21-46151724-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2357146.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000387 (59/152332) while in subpopulation AFR AF = 0.00135 (56/41582). AF 95% confidence interval is 0.00106. There are 0 homozygotes in GnomAd4. There are 24 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206965.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FTCD	NM_206965.2	MANE Select	c.470A>T	p.Asp157Val	missense	Exon 5 of 14	NP_996848.1	O95954-1
FTCD	NM_001320412.2		c.470A>T	p.Asp157Val	missense	Exon 5 of 15	NP_001307341.1	O95954-2
FTCD	NM_006657.3		c.470A>T	p.Asp157Val	missense	Exon 5 of 15	NP_006648.1	O95954-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FTCD	ENST00000397746.8	TSL:1 MANE Select	c.470A>T	p.Asp157Val	missense	Exon 5 of 14	ENSP00000380854.3	O95954-1
FTCD	ENST00000397748.5	TSL:1	c.470A>T	p.Asp157Val	missense	Exon 5 of 15	ENSP00000380856.1	O95954-2
FTCD	ENST00000291670.9	TSL:1	c.470A>T	p.Asp157Val	missense	Exon 5 of 15	ENSP00000291670.5	O95954-1

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000112

AC:

AN:

249362

AF XY:

0.0000517

show subpopulations

Gnomad AFR exome

AF:

0.00162

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1460512

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

726562

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111940

Other (OTH)

AF:

0.000133

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000387

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

41582

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.000344

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000124

AC:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Uncertain

0.66

Eigen

Benign

-0.087

Eigen_PC

Benign

0.0057

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.060

MetaSVM

Benign

-0.43

MutationAssessor

Benign

1.5

PhyloP100

4.1

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.30

Sift

Benign

0.070

Sift4G

Uncertain

0.050

Polyphen

0.17

Vest4

0.41

MVP

0.75

MPC

0.098

ClinPred

0.074

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

gMVP

0.58

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over