rs116089237

chr21-46151896-T-AchrNT_187626.1-10954-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_206965.2(FTCD):c.452A>T(p.Lys151Met) variant causes a missense change. The variant allele was found at a frequency of 0.00459 in 1,562,368 control chromosomes in the GnomAD database, including 260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (120 hom., cov: 34)
  • Exomes 𝑓: 0.0026 (140 hom.)
• Consequence: FTCD NM_206965.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.47

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004734993).
• BP6: Variant 21-46151896-T-A is Benign according to our data. Variant chr21-46151896-T-A is described in ClinVar as [Benign]. Clinvar id is 282697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FTCD	NM_206965.2	c.452A>T	p.Lys151Met	missense_variant	4/14	ENST00000397746.8
FTCD-AS1	NR_170989.1	n.146+137T>A		intron_variant, non_coding_transcript_variant
FTCD	NM_001320412.2	c.452A>T	p.Lys151Met	missense_variant	4/15
FTCD	NM_006657.3	c.452A>T	p.Lys151Met	missense_variant	4/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTCD	ENST00000397746.8	c.452A>T	p.Lys151Met	missense_variant	4/14	1	NM_206965.2	P1
FTCD-AS1	ENST00000446649.1	n.146+137T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0232 AC: 3536 AN: 152176 Hom.: 120 Cov.: 34

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.00544 AC: 913 AN: 167830 Hom.: 26 AF XY: 0.00441 AC XY: 401 AN XY: 90948

Gnomad AFR exome AF: 0.0848

Gnomad AMR exome AF: 0.00527

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000824

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000604

Gnomad OTH exome AF: 0.00306

GnomAD4 exome AF: 0.00257 AC: 3622 AN: 1410074 Hom.: 140 Cov.: 31 AF XY: 0.00225 AC XY: 1568 AN XY: 696976

Gnomad4 AFR exome AF: 0.0832

Gnomad4 AMR exome AF: 0.00595

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000124

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000325

Gnomad4 OTH exome AF: 0.00590

GnomAD4 genome AF: 0.0233 AC: 3544 AN: 152294 Hom.: 120 Cov.: 34 AF XY: 0.0223 AC XY: 1657 AN XY: 74470

Gnomad4 AFR AF: 0.0787

Gnomad4 AMR AF: 0.0135

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00791 Hom.: 10

Bravo AF: 0.0270

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0658 AC: 274

ESP6500EA AF: 0.000361 AC: 3

ExAC AF: 0.00554 AC: 645

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Aug 17, 2015

- -

Glutamate formiminotransferase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 14, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.33
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D;.;D;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.90	D
MetaRNN	Benign	0.0047	T;T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.2	M;M;M;.
MutationTaster	Benign	0.58	N;N;N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		0.86	P;P;P;P
Vest4		0.47
MVP		0.89
MPC		0.22
ClinPred		0.017	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs116089237; hg19: chr21-47571810;