rs374724805

chr21-46151970-G-AchrNT_187626.1-11028-G-Achr21-46151970-G-TchrNT_187626.1-11028-G-Tchr21-46151970-G-CchrNT_187626.1-11028-G-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_206965.2(FTCD):c.378C>T(p.Tyr126=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,566,116 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0029 (10 hom.)
• Consequence: FTCD NM_206965.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.517

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-AS1 (HGNC:40243): (FTCD antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 21-46151970-G-A is Benign according to our data. Variant chr21-46151970-G-A is described in ClinVar as [Benign]. Clinvar id is 340438.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.517 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FTCD	NM_206965.2	c.378C>T	p.Tyr126=	synonymous_variant	4/14	ENST00000397746.8
FTCD-AS1	NR_170989.1	n.146+211G>A		intron_variant, non_coding_transcript_variant
FTCD	NM_001320412.2	c.378C>T	p.Tyr126=	synonymous_variant	4/15
FTCD	NM_006657.3	c.378C>T	p.Tyr126=	synonymous_variant	4/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTCD	ENST00000397746.8	c.378C>T	p.Tyr126=	synonymous_variant	4/14	1	NM_206965.2	P1
FTCD-AS1	ENST00000446649.1	n.146+211G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00206 AC: 313 AN: 152200 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00309

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00219 AC: 371 AN: 169640 Hom.: 0 AF XY: 0.00225 AC XY: 207 AN XY: 91904

Gnomad AFR exome AF: 0.00158

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000418

Gnomad FIN exome AF: 0.00107

Gnomad NFE exome AF: 0.00343

Gnomad OTH exome AF: 0.00304

GnomAD4 exome AF: 0.00285 AC: 4032 AN: 1413798 Hom.: 10 Cov.: 31 AF XY: 0.00281 AC XY: 1967 AN XY: 699156

Gnomad4 AFR exome AF: 0.000928

Gnomad4 AMR exome AF: 0.00262

Gnomad4 ASJ exome AF: 0.00265

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000372

Gnomad4 FIN exome AF: 0.000844

Gnomad4 NFE exome AF: 0.00333

Gnomad4 OTH exome AF: 0.00265

GnomAD4 genome AF: 0.00205 AC: 313 AN: 152318 Hom.: 0 Cov.: 34 AF XY: 0.00175 AC XY: 130 AN XY: 74482

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.00309

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00179 Hom.: 0

Bravo AF: 0.00262

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Glutamate formiminotransferase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	0.060
Dann	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs374724805; hg19: chr21-47571884; COSMIC: COSV52426951;