9-127799409-T-C

Position:

• chr9-127799409-T-C

Variant summary

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

The ENST00000479147.6(FPGS):​n.216+4597T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,028 control chromosomes in the GnomAD database, including 13,529 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 0.42 (13529 hom., cov: 32)
• Consequence: FPGS ENST00000479147.6 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FPGS	ENST00000479147.6	n.216+4597T>C		intron_variant, non_coding_transcript_variant		5
FPGS	ENST00000479375.6	n.131+4597T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63309 AN: 151910 Hom.: 13524 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.429

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.417 AC: 63361 AN: 152028 Hom.: 13529 Cov.: 32 AF XY: 0.411 AC XY: 30539 AN XY: 74306

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.428

Alfa AF: 0.410 Hom.: 13200

Bravo AF: 0.433

Asia WGS AF: 0.480 AC: 1671 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12379987; hg19: chr9-130561688; COSMIC: COSV64675352;