chr4-9920546-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020041.3(SLC2A9):c.841G>C(p.Asp281His) variant causes a missense change. The variant allele was found at a frequency of 0.0237 in 1,614,140 control chromosomes in the GnomAD database, including 568 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. D281D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.019 ( 53 hom., cov: 33)

Exomes 𝑓: 0.024 ( 515 hom. )

Consequence

SLC2A9
NM_020041.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.62

Publications

18 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: 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

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=0.020402223).

BP6

Variant 4-9920546-C-G is Benign according to our data. Variant chr4-9920546-C-G is described in ClinVar as Benign. ClinVar VariationId is 350217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0187 (2852/152314) while in subpopulation NFE AF = 0.028 (1907/68026). AF 95% confidence interval is 0.027. There are 53 homozygotes in GnomAd4. There are 1432 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 53 AD,AR gene

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.841G>C	p.Asp281His	missense	Exon 7 of 12	NP_064425.2
	SLC2A9	NM_001001290.2		c.754G>C	p.Asp252His	missense	Exon 8 of 13	NP_001001290.1	Q9NRM0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC2A9	ENST00000264784.8	TSL:1 MANE Select	c.841G>C	p.Asp281His	missense	Exon 7 of 12	ENSP00000264784.3	Q9NRM0-1
SLC2A9	ENST00000309065.7	TSL:1	c.754G>C	p.Asp252His	missense	Exon 8 of 13	ENSP00000311383.3	Q9NRM0-2
SLC2A9	ENST00000505104.5	TSL:1	n.875G>C		non_coding_transcript_exon	Exon 8 of 12

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2853

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00391

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.00818

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0522

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0280

Gnomad OTH

AF:

0.0182

GnomAD2 exomes

AF:

0.0198

AC:

4962

AN:

251194

AF XY:

0.0196

show subpopulations

Gnomad AFR exome

AF:

0.00388

Gnomad AMR exome

AF:

0.00558

Gnomad ASJ exome

AF:

0.0129

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0472

Gnomad NFE exome

AF:

0.0297

Gnomad OTH exome

AF:

0.0163

GnomAD4 exome

AF:

0.0242

AC:

35354

AN:

1461826

Hom.:

515

Cov.:

AF XY:

0.0237

AC XY:

17210

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.00409

AC:

137

AN:

33480

American (AMR)

AF:

0.00566

AC:

253

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0133

AC:

347

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00254

AC:

219

AN:

86258

European-Finnish (FIN)

AF:

0.0480

AC:

2560

AN:

53362

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0275

AC:

30618

AN:

1112004

Other (OTH)

AF:

0.0200

AC:

1210

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

1997

3994

5991

7988

9985

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1084

2168

3252

4336

5420

<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:

0.0187

AC:

2852

AN:

152314

Hom.:

Cov.:

AF XY:

0.0192

AC XY:

1432

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00390

AC:

162

AN:

41572

American (AMR)

AF:

0.00817

AC:

125

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0124

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00166

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0522

AC:

554

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0280

AC:

1907

AN:

68026

Other (OTH)

AF:

0.0180

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

146

292

438

584

730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0262

Hom.:

Bravo

AF:

0.0146

TwinsUK

AF:

0.0218

AC:

ALSPAC

AF:

0.0306

AC:

118

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.0292

AC:

251

ExAC

AF:

0.0211

AC:

2560

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0222

EpiControl

AF:

0.0231

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Hypouricemia, renal, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

Eigen

Uncertain

0.35

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.020

MetaSVM

Uncertain

0.19

MutationAssessor

Pathogenic

3.3

PhyloP100

3.6

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.43

Sift

Benign

0.031

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.66

MPC

0.56

ClinPred

0.019

GERP RS

4.3

Varity_R

0.65

gMVP

0.70

Mutation Taster

=82/18

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over