rs3733589

Variant names:

• chr4-9985700-G-A
• rs3733589
• NM_020041.3:c.504C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-9985700-G-A
• chr4-9985700-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020041.3(SLC2A9):​c.504C>T​(p.Ile168Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.056 in 1,613,914 control chromosomes in the GnomAD database, including 6,141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.075 (766 hom., cov: 33)
  • Exomes 𝑓: 0.054 (5375 hom.)
• Consequence: SLC2A9 NM_020041.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.175

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 4-9985700-G-A is Benign according to our data. Variant chr4-9985700-G-A is described in ClinVar as [Benign]. Clinvar id is 350236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.175 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A9	NM_020041.3	c.504C>T	p.Ile168Ile	synonymous_variant	Exon 4 of 12	ENST00000264784.8	NP_064425.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A9	ENST00000264784.8	c.504C>T	p.Ile168Ile	synonymous_variant	Exon 4 of 12	1	NM_020041.3	ENSP00000264784.3

Frequencies

GnomAD3 genomes AF: 0.0745 AC: 11335 AN: 152152 Hom.: 763 Cov.: 33

Gnomad AFR AF: 0.0980

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0930

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0604

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0334

Gnomad OTH AF: 0.0646

GnomAD3 exomes AF: 0.0887 AC: 22257 AN: 251016 Hom.: 2062 AF XY: 0.0852 AC XY: 11563 AN XY: 135652

Gnomad AFR exome AF: 0.0998

Gnomad AMR exome AF: 0.114

Gnomad ASJ exome AF: 0.0586

Gnomad EAS exome AF: 0.395

Gnomad SAS exome AF: 0.102

Gnomad FIN exome AF: 0.0575

Gnomad NFE exome AF: 0.0355

Gnomad OTH exome AF: 0.0712

GnomAD4 exome AF: 0.0540 AC: 78973 AN: 1461644 Hom.: 5375 Cov.: 32 AF XY: 0.0550 AC XY: 40008 AN XY: 727132

Gnomad4 AFR exome AF: 0.0985

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.0588

Gnomad4 EAS exome AF: 0.410

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.0577

Gnomad4 NFE exome AF: 0.0324

Gnomad4 OTH exome AF: 0.0680

GnomAD4 genome AF: 0.0746 AC: 11364 AN: 152270 Hom.: 766 Cov.: 33 AF XY: 0.0794 AC XY: 5915 AN XY: 74454

Gnomad4 AFR AF: 0.0983

Gnomad4 AMR AF: 0.0929

Gnomad4 ASJ AF: 0.0542

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0604

Gnomad4 NFE AF: 0.0334

Gnomad4 OTH AF: 0.0682

Alfa AF: 0.0456 Hom.: 391

Bravo AF: 0.0798

Asia WGS AF: 0.203 AC: 706 AN: 3476

EpiCase AF: 0.0347

EpiControl AF: 0.0372

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 18, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypouricemia, renal, 2 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	3.2
DANN	Benign	0.67

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: rs3733589; hg19: chr4-9987324; COSMIC: COSV53316725;