rs757514010

Variant names:

• chr9-127803012-C-A
• rs757514010
• NM_004957.6:c.88C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-127803012-C-A
• chr9-127803012-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004957.6(FPGS):​c.88C>A​(p.Arg30Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000762 in 1,313,158 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: FPGS NM_004957.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.925
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.925 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004957.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FPGS	NM_004957.6	MANE Select	c.88C>A	p.Arg30Arg	synonymous	Exon 1 of 15	NP_004948.4
	FPGS	NM_001288803.1		c.88C>A	p.Arg30Arg	synonymous	Exon 1 of 14	NP_001275732.1	Q05932-4
	FPGS	NR_110170.1		n.155C>A		non_coding_transcript_exon	Exon 1 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FPGS	ENST00000373247.7	TSL:1 MANE Select	c.88C>A	p.Arg30Arg	synonymous	Exon 1 of 15	ENSP00000362344.2	Q05932-1
	FPGS	ENST00000460181.5	TSL:1	n.95C>A		non_coding_transcript_exon	Exon 1 of 15
	FPGS	ENST00000910448.1		c.88C>A	p.Arg30Arg	synonymous	Exon 1 of 16	ENSP00000580507.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.62e-7 AC: 1 AN: 1313158 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 646942

African (AFR) AF: 0.00 AC: 0 AN: 25976

American (AMR) AF: 0.00 AC: 0 AN: 24088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22560

East Asian (EAS) AF: 0.00 AC: 0 AN: 28570

South Asian (SAS) AF: 0.0000141 AC: 1 AN: 70774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3886

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1048896

Other (OTH) AF: 0.00 AC: 0 AN: 54348

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.67
PhyloP100		0.93
PromoterAI		0.093	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs757514010; hg19: chr9-130565291;