21-46137029-CTG-TCT

Variant names:

• chr21-46137029-CTG-TCT
• NM_206965.2:c.1582_1584delCAGinsAGA
• FTCD p.Gln528Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_206965.2(FTCD):​c.1582_1584delCAGinsAGA​(p.Gln528Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q528P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FTCD NM_206965.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• formiminoglutamic aciduria

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTCD	NM_206965.2	MANE Select	c.1582_1584delCAGinsAGA	p.Gln528Arg	missense	N/A	NP_996848.1	O95954-1
	FTCD	NM_001320412.2		c.1562_1564delCAGinsAGA	p.ProGly521GlnSer	missense	N/A	NP_001307341.1	O95954-2
	FTCD	NM_006657.3		c.1582_1584delCAGinsAGA	p.Gln528Arg	missense	N/A	NP_006648.1	O95954-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTCD	ENST00000397746.8	TSL:1 MANE Select	c.1582_1584delCAGinsAGA	p.Gln528Arg	missense	N/A	ENSP00000380854.3	O95954-1
	FTCD	ENST00000397748.5	TSL:1	c.1562_1564delCAGinsAGA	p.ProGly521GlnSer	missense	N/A	ENSP00000380856.1	O95954-2
	FTCD	ENST00000291670.9	TSL:1	c.1582_1584delCAGinsAGA	p.Gln528Arg	missense	N/A	ENSP00000291670.5	O95954-1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr21-47556943;