NM_018291.5:c.670+3204G>C

Variant names:

• chr1-59460280-G-C
• rs7533447
• NM_018291.5:c.670+3204G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018291.5(FGGY):​c.670+3204G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,958 control chromosomes in the GnomAD database, including 15,732 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 0.45 (15732 hom., cov: 31)
• Consequence: FGGY NM_018291.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84
• Publications: 0 publications found

Genes affected

FGGY (HGNC:25610): (FGGY carbohydrate kinase domain containing) This gene encodes a protein that phosphorylates carbohydrates such as ribulose, ribitol, and L-arabinitol. Genome-wide association studies in some populations have found an association between polymorphisms in this gene and sporadic amyotrophic lateral sclerosis, but studies of other populations have not been able to replicate this association. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018291.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGGY	NM_018291.5	MANE Select	c.670+3204G>C		intron	N/A	NP_060761.3
	FGGY	NM_001113411.2		c.670+3204G>C		intron	N/A	NP_001106882.1
	FGGY	NM_001350790.2		c.670+3204G>C		intron	N/A	NP_001337719.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGGY	ENST00000303721.12	TSL:1 MANE Select	c.670+3204G>C		intron	N/A	ENSP00000305922.8
	FGGY	ENST00000371218.8	TSL:1	c.670+3204G>C		intron	N/A	ENSP00000360262.4
	FGGY	ENST00000894285.1		c.670+3204G>C		intron	N/A	ENSP00000564344.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68631 AN: 151840 Hom.: 15710 Cov.: 31

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.452 AC: 68697 AN: 151958 Hom.: 15732 Cov.: 31 AF XY: 0.447 AC XY: 33181 AN XY: 74284

African (AFR) AF: 0.501 AC: 20767 AN: 41432

American (AMR) AF: 0.468 AC: 7149 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1607 AN: 3472

East Asian (EAS) AF: 0.277 AC: 1428 AN: 5158

South Asian (SAS) AF: 0.389 AC: 1873 AN: 4820

European-Finnish (FIN) AF: 0.387 AC: 4081 AN: 10556

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30215 AN: 67938

Other (OTH) AF: 0.471 AC: 995 AN: 2114

Alfa AF: 0.285 Hom.: 622

Bravo AF: 0.463

Asia WGS AF: 0.331 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.21
DANN	Benign	0.45
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs7533447; hg19: chr1-59925952;