1-9039877-G-C

Variant names:

• chr1-9039877-G-C
• rs779760381
• NM_003039.3:c.808C>G

Variant summary

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

The NM_003039.3(SLC2A5):​c.808C>G​(p.Arg270Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,460,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. R270W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: SLC2A5 NM_003039.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• Publications: 0 publications found

Genes affected

SLC2A5 (HGNC:11010): (solute carrier family 2 member 5) The protein encoded by this gene is a fructose transporter responsible for fructose uptake by the small intestine. The encoded protein also is necessary for the increase in blood pressure due to high dietary fructose consumption. [provided by RefSeq, Jun 2016]

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=0.09695351).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003039.3. 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
	SLC2A5	NM_003039.3	MANE Select	c.808C>G	p.Arg270Gly	missense	Exon 7 of 12	NP_003030.1	P22732-1
	SLC2A5	NM_001328619.2		c.808C>G	p.Arg270Gly	missense	Exon 8 of 13	NP_001315548.1	P22732-1
	SLC2A5	NM_001328620.2		c.676C>G	p.Arg226Gly	missense	Exon 7 of 12	NP_001315549.1	B4DG19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A5	ENST00000377424.9	TSL:1 MANE Select	c.808C>G	p.Arg270Gly	missense	Exon 7 of 12	ENSP00000366641.4	P22732-1
	SLC2A5	ENST00000941832.1		c.808C>G	p.Arg270Gly	missense	Exon 8 of 13	ENSP00000611891.1
	SLC2A5	ENST00000941833.1		c.808C>G	p.Arg270Gly	missense	Exon 8 of 13	ENSP00000611892.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1460184 Hom.: 0 Cov.: 33 AF XY: 0.00000826 AC XY: 6 AN XY: 726436

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111734

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.34
DANN	Benign	0.87
DEOGEN2	Uncertain	0.58	D
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.96	L
PhyloP100		-2.5
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.18
Sift	Benign	0.23	T
Sift4G	Benign	0.33	T
Polyphen		0.0010	B
Vest4		0.080
MutPred		0.57		Loss of methylation at R270 (P = 0.0091)
MVP		0.20
MPC		0.46
ClinPred		0.077	T
GERP RS		-11
Varity_R		0.075
gMVP		0.27
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: rs779760381; hg19: chr1-9099936;