rs376986639

chr21-46145555-C-TchrNT_187626.1-4613-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_206965.2(FTCD):c.1122G>A(p.Val374=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,544,448 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00055 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (2 hom.)
• Consequence: FTCD NM_206965.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.144

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 21-46145555-C-T is Benign according to our data. Variant chr21-46145555-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 340425.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.144 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FTCD	NM_206965.2	c.1122G>A	p.Val374=	synonymous_variant	10/14	ENST00000397746.8
FTCD	NM_001320412.2	c.1122G>A	p.Val374=	synonymous_variant	10/15
FTCD	NM_006657.3	c.1122G>A	p.Val374=	synonymous_variant	10/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTCD	ENST00000397746.8	c.1122G>A	p.Val374=	synonymous_variant	10/14	1	NM_206965.2	P1

Frequencies

GnomAD3 genomes AF: 0.000546 AC: 83 AN: 151884 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00108

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000562 AC: 82 AN: 145846 Hom.: 0 AF XY: 0.000539 AC XY: 42 AN XY: 77950

Gnomad AFR exome AF: 0.000127

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000884

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00129

Gnomad OTH exome AF: 0.000947

GnomAD4 exome AF: 0.00118 AC: 1645 AN: 1392564 Hom.: 2 Cov.: 32 AF XY: 0.00115 AC XY: 790 AN XY: 686552

Gnomad4 AFR exome AF: 0.000190

Gnomad4 AMR exome AF: 0.000253

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000885

Gnomad4 FIN exome AF: 0.0000219

Gnomad4 NFE exome AF: 0.00147

Gnomad4 OTH exome AF: 0.000658

GnomAD4 genome AF: 0.000546 AC: 83 AN: 151884 Hom.: 0 Cov.: 31 AF XY: 0.000539 AC XY: 40 AN XY: 74178

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00108

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000590 Hom.: 0

Bravo AF: 0.000518

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Glutamate formiminotransferase deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	1.3
Dann	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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

LitVar

Other links and lift over

dbSNP: rs376986639; hg19: chr21-47565469;