dbSNP rs34330923: FPGS:p.Leu81Leu (chr9-127804389-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_004957.6(FPGS):c.243G>A(p.Leu81Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,614,214 control chromosomes in the GnomAD database, including 200 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.011 ( 16 hom., cov: 32)

Exomes 𝑓: 0.013 ( 184 hom. )

Consequence

FPGS
NM_004957.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.187

Variant links:

Genes affected

FPGS (HGNC:3824): (folylpolyglutamate synthase) This gene encodes the folylpolyglutamate synthetase enzyme. This enzyme has a central role in establishing and maintaining both cytosolic and mitochondrial folylpolyglutamate concentrations and, therefore, is essential for folate homeostasis and the survival of proliferating cells. This enzyme catalyzes the ATP-dependent addition of glutamate moieties to folate and folate derivatives. Alternative splicing results in transcript variants encoding different isoforms. [provided by RefSeq, Jan 2014]

FPGS 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=-0.59).

BP7

Synonymous conserved (PhyloP=0.187 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FPGS	NM_004957.6 link	c.243G>A	p.Leu81Leu	synonymous_variant	Exon 2 of 15	ENST00000373247.7	NP_004948.4	Q05932-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FPGS	ENST00000373247.7 link	c.243G>A	p.Leu81Leu	synonymous_variant	Exon 2 of 15	1	NM_004957.6	ENSP00000362344.2		Q05932-1

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1747

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00889

Gnomad FIN

AF:

0.0396

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0150

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.0130

AC:

3274

AN:

251298

Hom.:

AF XY:

0.0129

AC XY:

1754

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.00497

Gnomad ASJ exome

AF:

0.00417

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00585

Gnomad FIN exome

AF:

0.0396

Gnomad NFE exome

AF:

0.0168

Gnomad OTH exome

AF:

0.0124

GnomAD4 exome

AF:

0.0135

AC:

19668

AN:

1461860

Hom.:

184

Cov.:

AF XY:

0.0133

AC XY:

9638

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00233

Gnomad4 AMR exome

AF:

0.00505

Gnomad4 ASJ exome

AF:

0.00360

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00620

Gnomad4 FIN exome

AF:

0.0382

Gnomad4 NFE exome

AF:

0.0144

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.0115

AC:

1745

AN:

152354

Hom.:

Cov.:

AF XY:

0.0126

AC XY:

940

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00209

Gnomad4 AMR

AF:

0.00856

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00869

Gnomad4 FIN

AF:

0.0396

Gnomad4 NFE

AF:

0.0150

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0116

Hom.:

Bravo

AF:

0.00926

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0122

EpiControl

AF:

0.0113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

5.9

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over