9-127800446-C-T

Variant names:

• chr9-127800446-C-T
• rs1544105
• ENST00000479147.6:n.217-3839C>T

Variant summary

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

The ENST00000479147.6(FPGS):​n.217-3839C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,998 control chromosomes in the GnomAD database, including 18,421 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 0.48 (18421 hom., cov: 32)
• Consequence: FPGS ENST00000479147.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12

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=-0.99).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FPGS	ENST00000479147.6	n.217-3839C>T		intron_variant	Intron 1 of 7	5
FPGS	ENST00000479375.6	n.132-3839C>T		intron_variant	Intron 1 of 7	5

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73309 AN: 151880 Hom.: 18396 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.483 AC: 73389 AN: 151998 Hom.: 18421 Cov.: 32 AF XY: 0.477 AC XY: 35424 AN XY: 74294

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.477

Alfa AF: 0.438 Hom.: 19375

Bravo AF: 0.504

Asia WGS AF: 0.518 AC: 1804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.16
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1544105; hg19: chr9-130562725;