4-9920506-C-G

Variant names:

• chr4-9920506-C-G
• rs3733591
• NM_020041.3:c.881G>C

Variant summary

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

The NM_020041.3(SLC2A9):​c.881G>C​(p.Arg294Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R294H) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC2A9 NM_020041.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 0 publications found

Genes affected

SLC2A9 (HGNC:13446): (solute carrier family 2 member 9) This gene encodes a member of the SLC2A facilitative glucose transporter family. Members of this family play a significant role in maintaining glucose homeostasis. The encoded protein may play a role in the development and survival of chondrocytes in cartilage matrices. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

SLC2A9 Gene-Disease associations (from GenCC):

• hypouricemia, renal, 2

  Inheritance: AR, AD, SD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• hereditary renal hypouricemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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_020041.3. 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
	SLC2A9	NM_020041.3	MANE Select	c.881G>C	p.Arg294Pro	missense	Exon 7 of 12	NP_064425.2
	SLC2A9	NM_001001290.2		c.794G>C	p.Arg265Pro	missense	Exon 8 of 13	NP_001001290.1	Q9NRM0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A9	ENST00000264784.8	TSL:1 MANE Select	c.881G>C	p.Arg294Pro	missense	Exon 7 of 12	ENSP00000264784.3	Q9NRM0-1
	SLC2A9	ENST00000309065.7	TSL:1	c.794G>C	p.Arg265Pro	missense	Exon 8 of 13	ENSP00000311383.3	Q9NRM0-2
	SLC2A9	ENST00000505104.5	TSL:1	n.915G>C		non_coding_transcript_exon	Exon 8 of 12

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	0.0053	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.37	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-0.029
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.54		Loss of MoRF binding (P = 0.0103)
MVP		0.63
MPC		0.58
ClinPred		0.93	D
GERP RS		1.6
Varity_R		0.74
gMVP		0.79
Mutation Taster		=81/19	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: rs3733591; hg19: chr4-9922130;