9-127813796-T-C

Position:

• chr9-127813796-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004957.6(FPGS):​c.*192T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 1,270,974 control chromosomes in the GnomAD database, including 116,866 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 0.45 (15675 hom., cov: 33)
  • Exomes 𝑓: 0.42 (101191 hom.)
• Consequence: FPGS NM_004957.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FPGS	NM_004957.6	c.*192T>C		3_prime_UTR_variant	15/15	ENST00000373247.7	NP_004948.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FPGS	ENST00000373247.7	c.*192T>C		3_prime_UTR_variant	15/15	1	NM_004957.6	ENSP00000362344.2

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68199 AN: 152032 Hom.: 15659 Cov.: 33

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.447

GnomAD4 exome AF: 0.421 AC: 471496 AN: 1118826 Hom.: 101191 Cov.: 33 AF XY: 0.420 AC XY: 223175 AN XY: 531204

Gnomad4 AFR exome AF: 0.522

Gnomad4 AMR exome AF: 0.459

Gnomad4 ASJ exome AF: 0.369

Gnomad4 EAS exome AF: 0.685

Gnomad4 SAS exome AF: 0.368

Gnomad4 FIN exome AF: 0.325

Gnomad4 NFE exome AF: 0.416

Gnomad4 OTH exome AF: 0.425

GnomAD4 genome AF: 0.449 AC: 68266 AN: 152148 Hom.: 15675 Cov.: 33 AF XY: 0.443 AC XY: 32974 AN XY: 74374

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.446

Alfa AF: 0.425 Hom.: 18469

Bravo AF: 0.469

Asia WGS AF: 0.513 AC: 1786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.74
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0

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

Other links and lift over

dbSNP: rs10106; hg19: chr9-130576075;