4-9980706-A-G

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.567T>C(p.Leu189Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 1,613,922 control chromosomes in the GnomAD database, including 497,654 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L189L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.73 ( 41623 hom., cov: 32)

Exomes 𝑓: 0.79 ( 456031 hom. )

Consequence

SLC2A9
NM_020041.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0220

Publications

33 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=-0.59).

BP6

Variant 4-9980706-A-G is Benign according to our data. Variant chr4-9980706-A-G is described in ClinVar as Benign. ClinVar VariationId is 350235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.022 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A9	NM_020041.3 link	c.567T>C	p.Leu189Leu	synonymous_variant	Exon 5 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.567T>C	p.Leu189Leu	synonymous_variant	Exon 5 of 12	1	NM_020041.3	ENSP00000264784.3		Q9NRM0-1

Frequencies

GnomAD3 genomes

AF:

0.733

AC:

111434

AN:

151980

Hom.:

41600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.601

Gnomad AMI

AF:

0.858

Gnomad AMR

AF:

0.653

Gnomad ASJ

AF:

0.734

Gnomad EAS

AF:

0.982

Gnomad SAS

AF:

0.773

Gnomad FIN

AF:

0.827

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.793

Gnomad OTH

AF:

0.745

GnomAD2 exomes

AF:

0.766

AC:

191718

AN:

250416

AF XY:

0.772

show subpopulations

Gnomad AFR exome

AF:

0.589

Gnomad AMR exome

AF:

0.609

Gnomad ASJ exome

AF:

0.741

Gnomad EAS exome

AF:

0.984

Gnomad FIN exome

AF:

0.828

Gnomad NFE exome

AF:

0.794

Gnomad OTH exome

AF:

0.772

GnomAD4 exome

AF:

0.787

AC:

1151063

AN:

1461824

Hom.:

456031

Cov.:

AF XY:

0.788

AC XY:

572692

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.593

AC:

19836

AN:

33478

American (AMR)

AF:

0.616

AC:

27541

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.746

AC:

19493

AN:

26136

East Asian (EAS)

AF:

0.988

AC:

39229

AN:

39698

South Asian (SAS)

AF:

0.761

AC:

65673

AN:

86254

European-Finnish (FIN)

AF:

0.832

AC:

44448

AN:

53412

Middle Eastern (MID)

AF:

0.756

AC:

4361

AN:

5768

European-Non Finnish (NFE)

AF:

0.794

AC:

883255

AN:

1111968

Other (OTH)

AF:

0.782

AC:

47227

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

14587

29174

43761

58348

72935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20696

41392

62088

82784

103480

<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:

0.733

AC:

111503

AN:

152098

Hom.:

41623

Cov.:

AF XY:

0.735

AC XY:

54624

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.601

AC:

24916

AN:

41456

American (AMR)

AF:

0.653

AC:

9986

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.734

AC:

2544

AN:

3468

East Asian (EAS)

AF:

0.981

AC:

5064

AN:

5160

South Asian (SAS)

AF:

0.773

AC:

3727

AN:

4820

European-Finnish (FIN)

AF:

0.827

AC:

8753

AN:

10586

Middle Eastern (MID)

AF:

0.772

AC:

227

AN:

294

European-Non Finnish (NFE)

AF:

0.793

AC:

53922

AN:

67996

Other (OTH)

AF:

0.748

AC:

1583

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1469

2938

4406

5875

7344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

844

1688

2532

3376

4220

<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:

0.767

Hom.:

129927

Bravo

AF:

0.715

Asia WGS

AF:

0.852

AC:

2961

AN:

3478

EpiCase

AF:

0.784

EpiControl

AF:

0.780

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypouricemia, renal, 2

Benign:2

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. -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

3.8

(source)

DANN

Benign

0.42

PhyloP100

-0.022

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

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

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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