1-9038877-G-C

Position:

• chr1-9038877-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003039.3(SLC2A5):​c.1049C>G​(p.Ser350Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SLC2A5 NM_003039.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.694

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37656862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A5	NM_003039.3	c.1049C>G	p.Ser350Cys	missense_variant	9/12	ENST00000377424.9	NP_003030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A5	ENST00000377424.9	c.1049C>G	p.Ser350Cys	missense_variant	9/12	1	NM_003039.3	ENSP00000366641.4
SLC2A5	ENST00000487492.1	n.397C>G		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460468 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726572

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2024

The c.1049C>G (p.S350C) alteration is located in exon 9 (coding exon 9) of the SLC2A5 gene. This alteration results from a C to G substitution at nucleotide position 1049, causing the serine (S) at amino acid position 350 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.57	D
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.22
Sift	Benign	0.046	D
Sift4G	Benign	0.076	T
Polyphen		0.92	P
Vest4		0.26
MutPred		0.66		Loss of catalytic residue at L346 (P = 0.1944);
MVP		0.77
MPC		0.36
ClinPred		0.40	T
GERP RS		1.4
Varity_R		0.15
gMVP		0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs1641214305; hg19: chr1-9098936;