chr1-74204397-A-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003838.5(FPGT):c.350A>G(p.Tyr117Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000391 in 1,559,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

FPGT
NM_003838.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.62

Publications

1 publications found

Variant links:

Genes affected

FPGT (HGNC:3825): (fucose-1-phosphate guanylyltransferase) L-fucose is a key sugar in glycoproteins and other complex carbohydrates since it may be involved in many of the functional roles of these macromolecules, such as in cell-cell recognition. The fucosyl donor for these fucosylated oligosaccharides is GDP-beta-L-fucose. There are two alternate pathways for the biosynthesis of GDP-fucose; the major pathway converts GDP-alpha-D-mannose to GDP-beta-L-fucose. The protein encoded by this gene participates in an alternate pathway that is present in certain mammalian tissues, such as liver and kidney, and appears to function as a salvage pathway to reutilize L-fucose arising from the turnover of glycoproteins and glycolipids. This pathway involves the phosphorylation of L-fucose to form beta-L-fucose-1-phosphate, and then condensation of the beta-L-fucose-1-phosphate with GTP by fucose-1-phosphate guanylyltransferase to form GDP-beta-L-fucose. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream TNNI3 interacting kinase (TNNI3K) gene. [provided by RefSeq, Dec 2010]

FPGT links:

FPGT-TNNI3K (HGNC:42952): (FPGT-TNNI3K readthrough) Enables protein C-terminus binding activity; protein kinase activity; and troponin I binding activity. Involved in protein phosphorylation and regulation of heart contraction. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FPGT-TNNI3K links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20390832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FPGT	NM_003838.5 link	c.350A>G	p.Tyr117Cys	missense_variant	Exon 4 of 4	ENST00000370898.9	NP_003829.4	O14772A0A0S2Z5C6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FPGT	ENST00000370898.9 link	c.350A>G	p.Tyr117Cys	missense_variant	Exon 4 of 4	1	NM_003838.5	ENSP00000359935.4		A0A0S2Z5C6
FPGT-TNNI3K	ENST00000557284.7 link	c.343+2987A>G		intron_variant	Intron 3 of 26	2		ENSP00000450895.3		V9GXZ4

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000658

AC:

AN:

212616

AF XY:

0.0000348

show subpopulations

Gnomad AFR exome

AF:

0.000901

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000220

AC:

AN:

1407430

Hom.:

Cov.:

AF XY:

0.0000215

AC XY:

AN XY:

697912

show subpopulations

African (AFR)

AF:

0.000639

AC:

AN:

31282

American (AMR)

AF:

0.00

AC:

AN:

34500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22978

East Asian (EAS)

AF:

0.00

AC:

AN:

39362

South Asian (SAS)

AF:

0.0000131

AC:

AN:

76556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51404

Middle Eastern (MID)

AF:

0.000729

AC:

AN:

5488

European-Non Finnish (NFE)

AF:

9.19e-7

AC:

AN:

1087706

Other (OTH)

AF:

0.0000860

AC:

AN:

58154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000197

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.000676

AC:

AN:

41448

American (AMR)

AF:

0.0000654

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000845

Hom.:

Bravo

AF:

0.000234

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000989

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.350A>G (p.Y117C) alteration is located in exon 4 (coding exon 4) of the FPGT gene. This alteration results from a A to G substitution at nucleotide position 350, causing the tyrosine (Y) at amino acid position 117 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.7

.;M;.

PhyloP100

6.6

PROVEAN

Pathogenic

-6.4

.;D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0010

.;D;T

Sift4G

Uncertain

0.0050

D;D;D

Vest4

0.69

MVP

0.45

ClinPred

0.50

GERP RS

4.5

Varity_R

0.12

gMVP

0.45

Mutation Taster

=54/46

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr1-74204397-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over