chr4-9908299-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020041.3(SLC2A9):c.1049C>T(p.Pro350Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 1,612,430 control chromosomes in the GnomAD database, including 199,977 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. P350P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.38 ( 13735 hom., cov: 31)

Exomes 𝑓: 0.50 ( 186242 hom. )

Consequence

SLC2A9
NM_020041.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.742

Publications

62 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.17807096E-4).

BP6

Variant 4-9908299-G-A is Benign according to our data. Variant chr4-9908299-G-A is described in ClinVar as Benign. ClinVar VariationId is 350207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.514 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.1049C>T	p.Pro350Leu	missense	Exon 8 of 12	NP_064425.2
	SLC2A9	NM_001001290.2		c.962C>T	p.Pro321Leu	missense	Exon 9 of 13	NP_001001290.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC2A9	ENST00000264784.8	TSL:1 MANE Select	c.1049C>T	p.Pro350Leu	missense	Exon 8 of 12	ENSP00000264784.3
SLC2A9	ENST00000309065.7	TSL:1	c.962C>T	p.Pro321Leu	missense	Exon 9 of 13	ENSP00000311383.3
SLC2A9	ENST00000505104.5	TSL:1	n.1083C>T		non_coding_transcript_exon	Exon 9 of 12

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57795

AN:

151858

Hom.:

13725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0988

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.413

Gnomad ASJ

AF:

0.553

Gnomad EAS

AF:

0.237

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.519

Gnomad OTH

AF:

0.384

GnomAD2 exomes

AF:

0.442

AC:

111078

AN:

251316

AF XY:

0.452

show subpopulations

Gnomad AFR exome

AF:

0.0895

Gnomad AMR exome

AF:

0.388

Gnomad ASJ exome

AF:

0.560

Gnomad EAS exome

AF:

0.227

Gnomad FIN exome

AF:

0.541

Gnomad NFE exome

AF:

0.519

Gnomad OTH exome

AF:

0.471

GnomAD4 exome

AF:

0.497

AC:

726551

AN:

1460454

Hom.:

186242

Cov.:

AF XY:

0.497

AC XY:

361048

AN XY:

726644

show subpopulations

African (AFR)

AF:

0.0812

AC:

2719

AN:

33466

American (AMR)

AF:

0.392

AC:

17527

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.555

AC:

14486

AN:

26116

East Asian (EAS)

AF:

0.284

AC:

11268

AN:

39694

South Asian (SAS)

AF:

0.422

AC:

36426

AN:

86222

European-Finnish (FIN)

AF:

0.541

AC:

28914

AN:

53414

Middle Eastern (MID)

AF:

0.460

AC:

2654

AN:

5764

European-Non Finnish (NFE)

AF:

0.526

AC:

584704

AN:

1110708

Other (OTH)

AF:

0.462

AC:

27853

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

16876

33752

50627

67503

84379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16478

32956

49434

65912

82390

<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:

0.380

AC:

57814

AN:

151976

Hom.:

13735

Cov.:

AF XY:

0.381

AC XY:

28317

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.0986

AC:

4089

AN:

41490

American (AMR)

AF:

0.412

AC:

6296

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.553

AC:

1920

AN:

3470

East Asian (EAS)

AF:

0.237

AC:

1226

AN:

5164

South Asian (SAS)

AF:

0.412

AC:

1983

AN:

4812

European-Finnish (FIN)

AF:

0.532

AC:

5598

AN:

10528

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.519

AC:

35256

AN:

67932

Other (OTH)

AF:

0.387

AC:

816

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1576

3153

4729

6306

7882

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.469

Hom.:

70302

Bravo

AF:

0.358

TwinsUK

AF:

0.533

AC:

1978

ALSPAC

AF:

0.516

AC:

1987

ESP6500AA

AF:

0.103

AC:

452

ESP6500EA

AF:

0.521

AC:

4482

ExAC

AF:

0.438

AC:

53130

Asia WGS

AF:

0.321

AC:

1112

AN:

3478

EpiCase

AF:

0.515

EpiControl

AF:

0.511

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Hypouricemia, renal, 2 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.17

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.76

MetaRNN

Benign

0.00012

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.94

PhyloP100

-0.74

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.13

Sift

Benign

0.34

Sift4G

Benign

0.28

Polyphen

0.064

Vest4

0.033

MPC

0.11

ClinPred

0.0065

GERP RS

0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.58

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over