chr9-127803598-C-T

Position:

• chr9-127803598-C-T

Variant summary

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

The NM_004957.6(FPGS):​c.138+536C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,936 control chromosomes in the GnomAD database, including 4,746 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 0.24 (4746 hom., cov: 31)
• Consequence: FPGS NM_004957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FPGS	NM_004957.6	c.138+536C>T		intron_variant		ENST00000373247.7	NP_004948.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FPGS	ENST00000373247.7	c.138+536C>T		intron_variant		1	NM_004957.6	ENSP00000362344	P1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36701 AN: 151818 Hom.: 4744 Cov.: 31

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.242 AC: 36716 AN: 151936 Hom.: 4746 Cov.: 31 AF XY: 0.251 AC XY: 18601 AN XY: 74236

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.199

Alfa AF: 0.240 Hom.: 1036

Bravo AF: 0.215

Asia WGS AF: 0.299 AC: 1038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.4
DANN	Benign	0.76

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: rs10987742; hg19: chr9-130565877;