21-46145803-T-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_206965.2(FTCD):​c.1098+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000098 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000081 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FTCD NM_206965.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 21-46145803-T-C is Benign according to our data. Variant chr21-46145803-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 402885.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Frequencies

GnomAD3 genomes AF: 0.0000979 AC: 4 AN: 40842 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000222

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000811 AC: 16 AN: 197254 Hom.: 0 Cov.: 7 AF XY: 0.0000908 AC XY: 9 AN XY: 99110

⚠️ 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: 3010

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

South Asian (SAS) AF: 0.000199 AC: 3 AN: 15046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8806

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 642

European-Non Finnish (NFE) AF: 0.0000837 AC: 12 AN: 143300

Other (OTH) AF: 0.00 AC: 0 AN: 8738

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0000978 AC: 4 AN: 40894 Hom.: 0 Cov.: 0 AF XY: 0.000153 AC XY: 3 AN XY: 19634

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

African (AFR) AF: 0.00 AC: 0 AN: 11240

American (AMR) AF: 0.00 AC: 0 AN: 4242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 942

East Asian (EAS) AF: 0.00 AC: 0 AN: 2068

South Asian (SAS) AF: 0.00 AC: 0 AN: 1236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 86

European-Non Finnish (NFE) AF: 0.000222 AC: 4 AN: 18056

Other (OTH) AF: 0.00 AC: 0 AN: 514

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000000294109), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00641 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.73
DANN	Benign	0.30
PhyloP100		-0.94

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

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;