10-133357993-C-T

Variant names:

• chr10-133357993-C-T
• rs749267993
• NM_001098483.3:c.15G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001098483.3(FUOM):​c.15G>A​(p.Lys5Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,357,456 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: 34)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: FUOM NM_001098483.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=-0.012 with no splicing effect.

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.15G>A	p.Lys5Lys	synonymous	Exon 1 of 6	NP_001091953.1	A2VDF0-1
	FUOM	NM_198472.3		c.15G>A	p.Lys5Lys	synonymous	Exon 1 of 6	NP_940874.2	A2VDF0-2
	FUOM	NM_001301827.2		c.15G>A	p.Lys5Lys	synonymous	Exon 1 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.15G>A	p.Lys5Lys	synonymous	Exon 1 of 6	ENSP00000278025.5	A2VDF0-1
	FUOM	ENST00000368552.8	TSL:1	c.15G>A	p.Lys5Lys	synonymous	Exon 1 of 6	ENSP00000357540.5	A2VDF0-2
	FUOM	ENST00000863242.1		c.15G>A	p.Lys5Lys	synonymous	Exon 1 of 6	ENSP00000533301.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1357456 Hom.: 0 Cov.: 32 AF XY: 0.00000149 AC XY: 1 AN XY: 669460

⚠️ 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: 27714

American (AMR) AF: 0.00 AC: 0 AN: 33096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24004

East Asian (EAS) AF: 0.00 AC: 0 AN: 31324

South Asian (SAS) AF: 0.00 AC: 0 AN: 76278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4040

European-Non Finnish (NFE) AF: 0.00000188 AC: 2 AN: 1065770

Other (OTH) AF: 0.00 AC: 0 AN: 56476

⚠️ 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 Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	7.6
DANN	Benign	0.95
PhyloP100		-0.012
PromoterAI		-0.084	Neutral

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: rs749267993; hg19: chr10-135171497;