chr10-133356699-C-G

Variant names:

• chr10-133356699-C-G
• rs1360433360
• NM_001098483.3:c.265G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001098483.3(FUOM):​c.265G>C​(p.Gly89Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,599,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G89V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FUOM NM_001098483.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0350
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2609647).

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.265G>C	p.Gly89Arg	missense	Exon 4 of 6	NP_001091953.1	A2VDF0-1
	FUOM	NM_198472.3		c.265G>C	p.Gly89Arg	missense	Exon 4 of 6	NP_940874.2	A2VDF0-2
	FUOM	NM_001301827.2		c.196G>C	p.Gly66Arg	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.265G>C	p.Gly89Arg	missense	Exon 4 of 6	ENSP00000278025.5	A2VDF0-1
	FUOM	ENST00000368552.8	TSL:1	c.265G>C	p.Gly89Arg	missense	Exon 4 of 6	ENSP00000357540.5	A2VDF0-2
	FUOM	ENST00000863242.1		c.265G>C	p.Gly89Arg	missense	Exon 4 of 6	ENSP00000533301.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000417 AC: 1 AN: 239616 AF XY: 0.00000770

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000924

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1447586 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 718014

⚠️ 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: 33140

American (AMR) AF: 0.00 AC: 0 AN: 43426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25768

East Asian (EAS) AF: 0.00 AC: 0 AN: 39316

South Asian (SAS) AF: 0.00 AC: 0 AN: 84720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5500

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1104286

Other (OTH) AF: 0.00 AC: 0 AN: 59642

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000313 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.064
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.42	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		0.035
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.23
Sift	Uncertain	0.020	D
Sift4G	Benign	0.094	T
Polyphen		0.98	D
Vest4		0.42
MutPred		0.56		Gain of solvent accessibility (P = 0.0014)
MVP		0.19
MPC		0.067
ClinPred		0.88	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.44
gMVP		0.57
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1360433360; hg19: chr10-135170203;