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. The variant received -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
• Publications: 23 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 -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 VariationId 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.

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.504C>T	p.Ile168Ile	synonymous	Exon 4 of 12	NP_064425.2
	SLC2A9	NM_001001290.2		c.417C>T	p.Ile139Ile	synonymous	Exon 5 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.504C>T	p.Ile168Ile	synonymous	Exon 4 of 12	ENSP00000264784.3	Q9NRM0-1
	SLC2A9	ENST00000309065.7	TSL:1	c.417C>T	p.Ile139Ile	synonymous	Exon 5 of 13	ENSP00000311383.3	Q9NRM0-2
	SLC2A9	ENST00000505104.5	TSL:1	n.538C>T		non_coding_transcript_exon	Exon 5 of 12

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

GnomAD2 exomes AF: 0.0887 AC: 22257 AN: 251016 AF XY: 0.0852

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 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

African (AFR) AF: 0.0985 AC: 3298 AN: 33470

American (AMR) AF: 0.115 AC: 5122 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0588 AC: 1537 AN: 26132

East Asian (EAS) AF: 0.410 AC: 16290 AN: 39696

South Asian (SAS) AF: 0.104 AC: 8966 AN: 86250

European-Finnish (FIN) AF: 0.0577 AC: 3081 AN: 53420

Middle Eastern (MID) AF: 0.0864 AC: 498 AN: 5762

European-Non Finnish (NFE) AF: 0.0324 AC: 36077 AN: 1111820

Other (OTH) AF: 0.0680 AC: 4104 AN: 60378

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

African (AFR) AF: 0.0983 AC: 4085 AN: 41556

American (AMR) AF: 0.0929 AC: 1421 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 188 AN: 3468

East Asian (EAS) AF: 0.390 AC: 2015 AN: 5162

South Asian (SAS) AF: 0.114 AC: 548 AN: 4826

European-Finnish (FIN) AF: 0.0604 AC: 641 AN: 10614

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0334 AC: 2270 AN: 68026

Other (OTH) AF: 0.0682 AC: 144 AN: 2112

Alfa AF: 0.0499 Hom.: 579

Bravo AF: 0.0798

Asia WGS AF: 0.203 AC: 706 AN: 3476

EpiCase AF: 0.0347

EpiControl AF: 0.0372

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
BayesDel_noAF	Benign	-0.53
CADD	Benign	3.2
DANN	Benign	0.67
PhyloP100		-0.17
Mutation Taster		=100/0	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: rs3733589; hg19: chr4-9987324; COSMIC: COSV53316725;