rs3733591

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-9920506-C-T
• chr4-9920506-C-A
• chr4-9920506-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020041.3(SLC2A9):​c.881G>A​(p.Arg294His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,614,018 control chromosomes in the GnomAD database, including 43,797 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R294R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.18 (3490 hom., cov: 33)
  • Exomes 𝑓: 0.21 (40307 hom.)
• Consequence: SLC2A9 NM_020041.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0290
• Publications: 90 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.065905E-6).
• BP6: Variant 4-9920506-C-T is Benign according to our data. Variant chr4-9920506-C-T is described in ClinVar as Benign. ClinVar VariationId is 350213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

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>A	p.Arg294His	missense	Exon 7 of 12	NP_064425.2
	SLC2A9	NM_001001290.2		c.794G>A	p.Arg265His	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>A	p.Arg294His	missense	Exon 7 of 12	ENSP00000264784.3	Q9NRM0-1
	SLC2A9	ENST00000309065.7	TSL:1	c.794G>A	p.Arg265His	missense	Exon 8 of 13	ENSP00000311383.3	Q9NRM0-2
	SLC2A9	ENST00000505104.5	TSL:1	n.915G>A		non_coding_transcript_exon	Exon 8 of 12

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27517 AN: 152118 Hom.: 3490 Cov.: 33

Gnomad AFR AF: 0.0689

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.178

GnomAD2 exomes AF: 0.246 AC: 61854 AN: 251088 AF XY: 0.252

Gnomad AFR exome AF: 0.0668

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.671

Gnomad FIN exome AF: 0.240

Gnomad NFE exome AF: 0.189

Gnomad OTH exome AF: 0.221

GnomAD4 exome AF: 0.214 AC: 313476 AN: 1461782 Hom.: 40307 Cov.: 38 AF XY: 0.219 AC XY: 159222 AN XY: 727190

African (AFR) AF: 0.0624 AC: 2090 AN: 33480

American (AMR) AF: 0.223 AC: 9958 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4239 AN: 26136

East Asian (EAS) AF: 0.691 AC: 27447 AN: 39698

South Asian (SAS) AF: 0.361 AC: 31132 AN: 86256

European-Finnish (FIN) AF: 0.240 AC: 12802 AN: 53356

Middle Eastern (MID) AF: 0.176 AC: 1017 AN: 5768

European-Non Finnish (NFE) AF: 0.190 AC: 211802 AN: 1111974

Other (OTH) AF: 0.215 AC: 12989 AN: 60394

GnomAD4 genome AF: 0.181 AC: 27522 AN: 152236 Hom.: 3490 Cov.: 33 AF XY: 0.190 AC XY: 14133 AN XY: 74442

African (AFR) AF: 0.0688 AC: 2860 AN: 41558

American (AMR) AF: 0.194 AC: 2961 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 508 AN: 3466

East Asian (EAS) AF: 0.662 AC: 3420 AN: 5166

South Asian (SAS) AF: 0.380 AC: 1834 AN: 4828

European-Finnish (FIN) AF: 0.243 AC: 2582 AN: 10606

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12794 AN: 68006

Other (OTH) AF: 0.181 AC: 383 AN: 2112

Alfa AF: 0.194 Hom.: 16777

Bravo AF: 0.171

TwinsUK AF: 0.201 AC: 746

ALSPAC AF: 0.186 AC: 717

ESP6500AA AF: 0.0713 AC: 314

ESP6500EA AF: 0.189 AC: 1629

ExAC AF: 0.245 AC: 29794

Asia WGS AF: 0.454 AC: 1573 AN: 3478

EpiCase AF: 0.188

EpiControl AF: 0.182

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Hypouricemia, renal, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.0000071	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.029
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.28
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.094
MPC		0.14
ClinPred		0.022	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.43
Mutation Taster		=98/2	polymorphism (auto)

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; COSMIC: COSV53319201; COSMIC: COSV53319201;