21-46145803-T-A

Variant names:

• chr21-46145803-T-A
• rs1060499859
• NM_206965.2:c.1098+15A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_206965.2(FTCD):​c.1098+15A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: 0)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: FTCD NM_206965.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942
• 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: Laboratory for Molecular Medicine, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.1098+15A>T		intron	N/A	NP_996848.1	O95954-1
	FTCD	NM_001320412.2		c.1098+15A>T		intron	N/A	NP_001307341.1	O95954-2
	FTCD	NM_006657.3		c.1098+15A>T		intron	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.1098+15A>T		intron	N/A	ENSP00000380854.3	O95954-1
	FTCD	ENST00000397748.5	TSL:1	c.1098+15A>T		intron	N/A	ENSP00000380856.1	O95954-2
	FTCD	ENST00000291670.9	TSL:1	c.1098+15A>T		intron	N/A	ENSP00000291670.5	O95954-1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.000112 AC: 22 AN: 197242 Hom.: 0 Cov.: 7 AF XY: 0.000101 AC XY: 10 AN XY: 99100

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 4610

American (AMR) AF: 0.00 AC: 0 AN: 2352

Ashkenazi Jewish (ASJ) AF: 0.000332 AC: 1 AN: 3008

East Asian (EAS) AF: 0.00 AC: 0 AN: 10750

South Asian (SAS) AF: 0.0000664 AC: 1 AN: 15050

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 644

European-Non Finnish (NFE) AF: 0.000140 AC: 20 AN: 143288

Other (OTH) AF: 0.00 AC: 0 AN: 8736

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.63
DANN	Benign	0.48
PhyloP100		-0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

dbSNP: rs1060499859;

hg19: chr21-47565717;