ENST00000397748.5:c.*70C>G

Variant names:

• chr21-46136384-G-C
• rs886057173
• ENST00000397748.5:c.*70C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000397748.5(FTCD):​c.*70C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,395,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 30)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: FTCD ENST00000397748.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Laboratory for Molecular Medicine, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397748.5. 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_001320412.2		c.*70C>G		3_prime_UTR	Exon 15 of 15	NP_001307341.1	O95954-2
	FTCD	NM_006657.3		c.*113C>G		3_prime_UTR	Exon 15 of 15	NP_006648.1	O95954-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTCD	ENST00000397748.5	TSL:1	c.*70C>G		3_prime_UTR	Exon 15 of 15	ENSP00000380856.1	O95954-2
	FTCD	ENST00000291670.9	TSL:1	c.*113C>G		3_prime_UTR	Exon 15 of 15	ENSP00000291670.5	O95954-1
	FTCD	ENST00000460011.6	TSL:1	n.*183C>G		non_coding_transcript_exon	Exon 5 of 5	ENSP00000507070.1	Q49AR5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1395346 Hom.: 0 Cov.: 24 AF XY: 0.00000145 AC XY: 1 AN XY: 691730

African (AFR) AF: 0.00 AC: 0 AN: 32170

American (AMR) AF: 0.00 AC: 0 AN: 43998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25508

East Asian (EAS) AF: 0.00 AC: 0 AN: 38786

South Asian (SAS) AF: 0.00 AC: 0 AN: 84134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51818

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 9.47e-7 AC: 1 AN: 1055554

Other (OTH) AF: 0.00 AC: 0 AN: 57754

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.61
DANN	Benign	0.45
PhyloP100		-1.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs886057173; hg19: chr21-47556298;