chr4-9985700-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.175

Publications

23 publications found

Variant links:

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: AD, AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
hereditary renal hypouricemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLC2A9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A9	NM_020041.3 link	c.504C>T	p.Ile168Ile	synonymous_variant	Exon 4 of 12	ENST00000264784.8	NP_064425.2	Q9NRM0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A9	ENST00000264784.8 link	c.504C>T	p.Ile168Ile	synonymous_variant	Exon 4 of 12	1	NM_020041.3	ENSP00000264784.3		Q9NRM0-1

Frequencies

GnomAD3 genomes

AF:

0.0745

AC:

11335

AN:

152152

Hom.:

763

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0550

AC XY:

40008

AN XY:

727132

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

4562

9123

13685

18246

22808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1660

3320

4980

6640

8300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0746

AC:

11364

AN:

152270

Hom.:

766

Cov.:

AF XY:

0.0794

AC XY:

5915

AN XY:

74454

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0334

AC:

2270

AN:

68026

Other (OTH)

AF:

0.0682

AC:

144

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

521

1043

1564

2086

2607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 18, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

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

(source)

DANN

Benign

0.67

PhyloP100

-0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over