rs10118903

Positions:

• chr9-127802768-C-T

Variant summary

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

The ENST00000479147.6(FPGS):​n.217-1517C>T 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 0.0147 in 649,534 control chromosomes in the GnomAD database, including 673 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 0.056 (521 hom., cov: 25)
  • Exomes 𝑓: 0.0051 (152 hom.)
• Consequence: FPGS ENST00000479147.6 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FPGS	ENST00000479147.6	n.217-1517C>T		intron_variant, non_coding_transcript_variant		5
FPGS	ENST00000479375.6	n.132-1517C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0559 AC: 6820 AN: 121954 Hom.: 516 Cov.: 25

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0256

Gnomad ASJ AF: 0.00196

Gnomad EAS AF: 0.00291

Gnomad SAS AF: 0.0377

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0236

Gnomad NFE AF: 0.000946

Gnomad OTH AF: 0.0458

GnomAD4 exome AF: 0.00509 AC: 2686 AN: 527492 Hom.: 152 AF XY: 0.00480 AC XY: 1245 AN XY: 259458

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.0165

Gnomad4 ASJ exome AF: 0.00202

Gnomad4 EAS exome AF: 0.000230

Gnomad4 SAS exome AF: 0.0234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000440

Gnomad4 OTH exome AF: 0.0121

GnomAD4 genome AF: 0.0560 AC: 6832 AN: 122042 Hom.: 521 Cov.: 25 AF XY: 0.0572 AC XY: 3267 AN XY: 57088

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.0256

Gnomad4 ASJ AF: 0.00196

Gnomad4 EAS AF: 0.00291

Gnomad4 SAS AF: 0.0370

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000946

Gnomad4 OTH AF: 0.0453

Alfa AF: 0.0375 Hom.: 61

Bravo AF: 0.0543

Asia WGS AF: 0.0300 AC: 104 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10118903; hg19: chr9-130565047;