rs61729373

Variant names:

• chr21-46151966-C-T
• rs61729373
• NM_206965.2:c.382G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-46151966-C-T
• chr21-46151966-C-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_206965.2(FTCD):​c.382G>A​(p.Glu128Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00215 in 1,566,986 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0022 (4 hom.)
• Consequence: FTCD NM_206965.2 missense
• Clinical Significance: Benign criteria provided, single submitter U:1 B:2
• Conservation: PhyloP100: 5.56
• Publications: 5 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-AS1 (HGNC:40243): (FTCD antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017312586).
• BP6: Variant 21-46151966-C-T is Benign according to our data. Variant chr21-46151966-C-T is described in ClinVar as Benign. ClinVar VariationId is 340437.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00149 (227/152336) while in subpopulation NFE AF = 0.00273 (186/68018). AF 95% confidence interval is 0.00241. There are 0 homozygotes in GnomAd4. There are 104 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

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.382G>A	p.Glu128Lys	missense	Exon 4 of 14	NP_996848.1	O95954-1
	FTCD	NM_001320412.2		c.382G>A	p.Glu128Lys	missense	Exon 4 of 15	NP_001307341.1	O95954-2
	FTCD	NM_006657.3		c.382G>A	p.Glu128Lys	missense	Exon 4 of 15	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.382G>A	p.Glu128Lys	missense	Exon 4 of 14	ENSP00000380854.3	O95954-1
	FTCD	ENST00000397748.5	TSL:1	c.382G>A	p.Glu128Lys	missense	Exon 4 of 15	ENSP00000380856.1	O95954-2
	FTCD	ENST00000291670.9	TSL:1	c.382G>A	p.Glu128Lys	missense	Exon 4 of 15	ENSP00000291670.5	O95954-1

Frequencies

GnomAD3 genomes AF: 0.00148 AC: 226 AN: 152218 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00273

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00189 AC: 322 AN: 170660 AF XY: 0.00212

Gnomad AFR exome AF: 0.000112

Gnomad AMR exome AF: 0.000226

Gnomad ASJ exome AF: 0.000696

Gnomad EAS exome AF: 0.000475

Gnomad FIN exome AF: 0.00138

Gnomad NFE exome AF: 0.00367

Gnomad OTH exome AF: 0.00259

GnomAD4 exome AF: 0.00222 AC: 3141 AN: 1414650 Hom.: 4 Cov.: 31 AF XY: 0.00219 AC XY: 1529 AN XY: 699604

African (AFR) AF: 0.000278 AC: 9 AN: 32342

American (AMR) AF: 0.000369 AC: 14 AN: 37900

Ashkenazi Jewish (ASJ) AF: 0.000947 AC: 24 AN: 25334

East Asian (EAS) AF: 0.000216 AC: 8 AN: 37022

South Asian (SAS) AF: 0.000545 AC: 44 AN: 80706

European-Finnish (FIN) AF: 0.00195 AC: 95 AN: 48658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 0.00263 AC: 2859 AN: 1088440

Other (OTH) AF: 0.00150 AC: 88 AN: 58586

GnomAD4 genome AF: 0.00149 AC: 227 AN: 152336 Hom.: 0 Cov.: 34 AF XY: 0.00140 AC XY: 104 AN XY: 74486

African (AFR) AF: 0.000313 AC: 13 AN: 41580

American (AMR) AF: 0.000327 AC: 5 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4834

European-Finnish (FIN) AF: 0.000753 AC: 8 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00273 AC: 186 AN: 68018

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00231 Hom.: 2

Bravo AF: 0.00147

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00248 AC: 21

ExAC AF: 0.00206 AC: 240

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	FTCD-related disorder (1)
-	-	1	Glutamate formiminotransferase deficiency (1)
-	1	-	Intellectual disability (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.94	L
PhyloP100		5.6
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.21
Sift	Benign	0.31	T
Sift4G	Benign	0.62	T
Polyphen		0.11	B
Vest4		0.58
MVP		0.82
MPC		0.071
ClinPred		0.033	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.82
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs61729373; hg19: chr21-47571880; COSMIC: COSV99385682;