1-59357572-C-T

Variant names:

• chr1-59357572-C-T
• rs835441
• NM_018291.5:c.465+11174C>T

Variant summary

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

The NM_018291.5(FGGY):​c.465+11174C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 151,902 control chromosomes in the GnomAD database, including 8,538 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 0.32 (8538 hom., cov: 32)
• Consequence: FGGY NM_018291.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGGY	NM_018291.5	c.465+11174C>T		intron_variant	Intron 4 of 15	ENST00000303721.12	NP_060761.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGGY	ENST00000303721.12	c.465+11174C>T		intron_variant	Intron 4 of 15	1	NM_018291.5	ENSP00000305922.8

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48314 AN: 151784 Hom.: 8526 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.318 AC: 48380 AN: 151902 Hom.: 8538 Cov.: 32 AF XY: 0.326 AC XY: 24167 AN XY: 74230

African (AFR) AF: 0.462 AC: 19151 AN: 41418

American (AMR) AF: 0.321 AC: 4896 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 788 AN: 3470

East Asian (EAS) AF: 0.413 AC: 2129 AN: 5152

South Asian (SAS) AF: 0.362 AC: 1741 AN: 4812

European-Finnish (FIN) AF: 0.337 AC: 3546 AN: 10524

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15236 AN: 67958

Other (OTH) AF: 0.282 AC: 595 AN: 2112

Alfa AF: 0.283 Hom.: 1120

Bravo AF: 0.321

Asia WGS AF: 0.385 AC: 1342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.42
DANN	Benign	0.34
PhyloP100		-1.1
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: rs835441; hg19: chr1-59823244;