10-133356648-C-A

Variant names:

• chr10-133356648-C-A
• rs775562649
• NM_001098483.3:c.316G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001098483.3(FUOM):​c.316G>T​(p.Gly106Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,578 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G106S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: FUOM NM_001098483.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 0 publications found

Genes affected

FUOM (HGNC:24733): (fucose mutarotase) Predicted to enable L-fucose mutarotase activity and fucose binding activity. Predicted to be involved in fucose metabolic process and fucosylation. Predicted to act upstream of or within female mating behavior and negative regulation of neuron differentiation. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098483.3. 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
	FUOM	NM_001098483.3	MANE Select	c.316G>T	p.Gly106Cys	missense	Exon 4 of 6	NP_001091953.1	A2VDF0-1
	FUOM	NM_198472.3		c.316G>T	p.Gly106Cys	missense	Exon 4 of 6	NP_940874.2	A2VDF0-2
	FUOM	NM_001301827.2		c.247G>T	p.Gly83Cys	missense	Exon 3 of 5	NP_001288756.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUOM	ENST00000278025.9	TSL:1 MANE Select	c.316G>T	p.Gly106Cys	missense	Exon 4 of 6	ENSP00000278025.5	A2VDF0-1
	FUOM	ENST00000368552.8	TSL:1	c.316G>T	p.Gly106Cys	missense	Exon 4 of 6	ENSP00000357540.5	A2VDF0-2
	FUOM	ENST00000863242.1		c.316G>T	p.Gly106Cys	missense	Exon 4 of 6	ENSP00000533301.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1422578 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 702704

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32372

American (AMR) AF: 0.0000250 AC: 1 AN: 40060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24708

East Asian (EAS) AF: 0.00 AC: 0 AN: 38788

South Asian (SAS) AF: 0.00 AC: 0 AN: 82080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1089134

Other (OTH) AF: 0.00 AC: 0 AN: 58592

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.13
Eigen_PC	Benign	-0.064
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.31	T
MutationAssessor	Pathogenic	3.9	H
PhyloP100		1.3
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.17
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.011	D
Polyphen		0.99	D
Vest4		0.48
MutPred		0.68		Loss of methylation at R109 (P = 0.0657)
MVP		0.17
MPC		0.22
ClinPred		0.99	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.39
gMVP		0.64
Mutation Taster		=93/7	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: rs775562649; hg19: chr10-135170152;