21-46136879-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_206965.2(FTCD):c.*108G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 1,570,760 control chromosomes in the GnomAD database, including 374,830 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (31453 hom., cov: 32)
  • Exomes 𝑓: 0.69 (343377 hom.)
• Consequence: FTCD NM_206965.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.742

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 21-46136879-C-T is Benign according to our data. Variant chr21-46136879-C-T is described in ClinVar as [Benign]. Clinvar id is 1285284.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FTCD	NM_206965.2	c.*108G>A		3_prime_UTR_variant	14/14	ENST00000397746.8
FTCD	NM_001320412.2	c.1678+36G>A		intron_variant
FTCD	NM_006657.3	c.*2+106G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTCD	ENST00000397746.8	c.*108G>A		3_prime_UTR_variant	14/14	1	NM_206965.2	P1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96009 AN: 151932 Hom.: 31436 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.655

GnomAD3 exomes AF: 0.654 AC: 117275 AN: 179344 Hom.: 39508 AF XY: 0.642 AC XY: 62373 AN XY: 97188

Gnomad AFR exome AF: 0.458

Gnomad AMR exome AF: 0.779

Gnomad ASJ exome AF: 0.724

Gnomad EAS exome AF: 0.515

Gnomad SAS exome AF: 0.443

Gnomad FIN exome AF: 0.665

Gnomad NFE exome AF: 0.715

Gnomad OTH exome AF: 0.692

GnomAD4 exome AF: 0.690 AC: 979281 AN: 1418710 Hom.: 343377 Cov.: 53 AF XY: 0.683 AC XY: 479096 AN XY: 701894

Gnomad4 AFR exome AF: 0.454

Gnomad4 AMR exome AF: 0.775

Gnomad4 ASJ exome AF: 0.727

Gnomad4 EAS exome AF: 0.496

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.666

Gnomad4 NFE exome AF: 0.721

Gnomad4 OTH exome AF: 0.674

GnomAD4 genome AF: 0.632 AC: 96057 AN: 152050 Hom.: 31453 Cov.: 32 AF XY: 0.626 AC XY: 46551 AN XY: 74356

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.724

Gnomad4 ASJ AF: 0.724

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.722

Gnomad4 OTH AF: 0.649

Alfa AF: 0.684 Hom.: 17806

Bravo AF: 0.634

Asia WGS AF: 0.517 AC: 1798 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Glutamate formiminotransferase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.4
Dann	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs12774; hg19: chr21-47556793; COSMIC: COSV52424167; COSMIC: COSV52424167;