21-46136370-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001320412.2(FTCD):c.*84C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,467,494 control chromosomes in the GnomAD database, including 7 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 0.0016 ( 1 hom., cov: 30)

Exomes 𝑓: 0.0022 ( 6 hom. )

Consequence

FTCD
NM_001320412.2 3_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 1.11

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 21-46136370-G-T is Benign according to our data. Variant chr21-46136370-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 340405.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00158 (241/152292) while in subpopulation NFE AF= 0.00297 (202/68030). AF 95% confidence interval is 0.00263. There are 1 homozygotes in gnomad4. There are 105 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTCD	NM_001320412.2 link	c.*84C>A		3_prime_UTR_variant	Exon 15 of 15		NP_001307341.1	O95954-2
FTCD	NM_006657.3 link	c.*127C>A		3_prime_UTR_variant	Exon 15 of 15		NP_006648.1	O95954-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
FTCD	ENST00000397748 link	c.*84C>A	3_prime_UTR_variant	Exon 15 of 15	1	ENSP00000380856.1	O95954-2
FTCD	ENST00000291670 link	c.*127C>A	3_prime_UTR_variant	Exon 15 of 15	1	ENSP00000291670.5	O95954-1
FTCD	ENST00000460011.6 link	n.*197C>A	non_coding_transcript_exon_variant	Exon 5 of 5	1	ENSP00000507070.1	Q49AR5

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

241

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00297

Gnomad OTH

AF:

0.000955

GnomAD4 exome

AF:

0.00221

AC:

2905

AN:

1315202

Hom.:

Cov.:

AF XY:

0.00213

AC XY:

1393

AN XY:

653136

show subpopulations

Gnomad4 AFR exome

AF:

0.000424

Gnomad4 AMR exome

AF:

0.000162

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000974

Gnomad4 NFE exome

AF:

0.00285

Gnomad4 OTH exome

AF:

0.00133

GnomAD4 genome

AF:

0.00158

AC:

241

AN:

152292

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00297

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000425

Hom.:

Bravo

AF:

0.00158

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Glutamate formiminotransferase deficiency

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Myosclerosis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Collagen 6-related myopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

COL6A2-related disorder

Benign:1

Sep 07, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.3

DANN

Benign

0.66

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