NM_206965.2:c.1166C>T

Variant names:

• chr21-46145511-G-A
• NM_206965.2:c.1166C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_206965.2(FTCD):​c.1166C>T​(p.Thr389Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FTCD NM_206965.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08080667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTCD	NM_206965.2	c.1166C>T	p.Thr389Met	missense_variant	Exon 10 of 14	ENST00000397746.8	NP_996848.1
FTCD	NM_001320412.2	c.1166C>T	p.Thr389Met	missense_variant	Exon 10 of 15		NP_001307341.1
FTCD	NM_006657.3	c.1166C>T	p.Thr389Met	missense_variant	Exon 10 of 15		NP_006648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTCD	ENST00000397746.8	c.1166C>T	p.Thr389Met	missense_variant	Exon 10 of 14	1	NM_206965.2	ENSP00000380854.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1398664 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 690226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.074	T;.;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.82	.;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.081	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;L;.
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.52	N;N;N;N
REVEL	Benign	0.023
Sift	Benign	0.094	T;T;T;T
Sift4G	Benign	0.10	T;T;T;T
Polyphen		0.083	B;B;B;B
Vest4		0.18
MutPred		0.37		Loss of phosphorylation at T389 (P = 0.0616);Loss of phosphorylation at T389 (P = 0.0616);Loss of phosphorylation at T389 (P = 0.0616);Loss of phosphorylation at T389 (P = 0.0616);
MVP		0.30
MPC		0.065
ClinPred		0.045	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.018
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-47565425; COSMIC: COSV52424493; COSMIC: COSV52424493;