Variant 21-46136430-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001320412.2(FTCD):c.*24C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00263 in 1,612,436 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0028 ( 8 hom. )

Consequence

FTCD
NM_001320412.2 3_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -1.71

Variant links:

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 links:

FTCD (HGNC:):

FTCD links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 21-46136430-G-A is Benign according to our data. Variant chr21-46136430-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 340408.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FTCD	NM_001320412.2 linkuse as main transcript	c.*24C>T		3_prime_UTR_variant	15/15		NP_001307341.1	O95954-2
FTCD	NM_006657.3 linkuse as main transcript	c.*67C>T		3_prime_UTR_variant	15/15		NP_006648.1	O95954-1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
FTCD	ENST00000397748 linkuse as main transcript	c.*24C>T	3_prime_UTR_variant	15/15	1	ENSP00000380856.1	O95954-2
FTCD	ENST00000291670 linkuse as main transcript	c.*67C>T	3_prime_UTR_variant	15/15	1	ENSP00000291670.5	O95954-1
FTCD	ENST00000460011.6 linkuse as main transcript	n.*137C>T	non_coding_transcript_exon_variant	5/5	1	ENSP00000507070.1	Q49AR5

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

202

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00221

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00153

AC:

372

AN:

243158

Hom.:

AF XY:

0.00146

AC XY:

195

AN XY:

133604

show subpopulations

Gnomad AFR exome

AF:

0.000633

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00172

Gnomad NFE exome

AF:

0.00248

Gnomad OTH exome

AF:

0.00184

GnomAD4 exome

AF:

0.00276

AC:

4032

AN:

1460218

Hom.:

Cov.:

AF XY:

0.00257

AC XY:

1865

AN XY:

726420

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.00148

Gnomad4 NFE exome

AF:

0.00332

Gnomad4 OTH exome

AF:

0.00240

GnomAD4 genome

AF:

0.00133

AC:

203

AN:

152218

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000554

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00221

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000431

Hom.:

Bravo

AF:

0.00157

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Glutamate formiminotransferase deficiency

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Myosclerosis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Collagen 6-related myopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.94

DANN

Benign

0.49

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over