rs16890979

Positions:

chr4-9920543-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020041.3(SLC2A9):c.844G>A(p.Val282Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,613,968 control chromosomes in the GnomAD database, including 46,504 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6967 hom., cov: 33)

Exomes 𝑓: 0.22 ( 39537 hom. )

Consequence

SLC2A9
NM_020041.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.76

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027513742).

BP6

Variant 4-9920543-C-T is Benign according to our data. Variant chr4-9920543-C-T is described in ClinVar as [Benign]. Clinvar id is 350215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A9	NM_020041.3 linkuse as main transcript	c.844G>A	p.Val282Ile	missense_variant	7/12	ENST00000264784.8	NP_064425.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A9	ENST00000264784.8 linkuse as main transcript	c.844G>A	p.Val282Ile	missense_variant	7/12	1	NM_020041.3	ENSP00000264784	A2	Q9NRM0-1
SLC2A9	ENST00000309065.7 linkuse as main transcript	c.757G>A	p.Val253Ile	missense_variant	8/13	1		ENSP00000311383	P2	Q9NRM0-2
SLC2A9	ENST00000505104.5 linkuse as main transcript	n.878G>A		non_coding_transcript_exon_variant	8/12	1
SLC2A9	ENST00000506583.5 linkuse as main transcript	c.757G>A	p.Val253Ile	missense_variant	9/14	5		ENSP00000422209	P2	Q9NRM0-2

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42936

AN:

152072

Hom.:

6956

Cov.:

show subpopulations

Gnomad AFR

AF:

0.428

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.0187

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.267

GnomAD3 exomes

AF:

0.243

AC:

61149

AN:

251162

Hom.:

8893

AF XY:

0.236

AC XY:

32097

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.439

Gnomad AMR exome

AF:

0.398

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.0158

Gnomad SAS exome

AF:

0.242

Gnomad FIN exome

AF:

0.183

Gnomad NFE exome

AF:

0.218

Gnomad OTH exome

AF:

0.234

GnomAD4 exome

AF:

0.224

AC:

327053

AN:

1461778

Hom.:

39537

Cov.:

AF XY:

0.223

AC XY:

162344

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.435

Gnomad4 AMR exome

AF:

0.392

Gnomad4 ASJ exome

AF:

0.233

Gnomad4 EAS exome

AF:

0.0117

Gnomad4 SAS exome

AF:

0.242

Gnomad4 FIN exome

AF:

0.180

Gnomad4 NFE exome

AF:

0.218

Gnomad4 OTH exome

AF:

0.228

GnomAD4 genome

AF:

0.282

AC:

42983

AN:

152190

Hom.:

6967

Cov.:

AF XY:

0.279

AC XY:

20794

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.428

Gnomad4 AMR

AF:

0.361

Gnomad4 ASJ

AF:

0.250

Gnomad4 EAS

AF:

0.0189

Gnomad4 SAS

AF:

0.229

Gnomad4 FIN

AF:

0.182

Gnomad4 NFE

AF:

0.220

Gnomad4 OTH

AF:

0.265

Alfa

AF:

0.231

Hom.:

6025

Bravo

AF:

0.300

TwinsUK

AF:

0.227

AC:

841

ALSPAC

AF:

0.209

AC:

805

ESP6500AA

AF:

0.414

AC:

1826

ESP6500EA

AF:

0.221

AC:

1898

ExAC

AF:

0.239

AC:

28971

Asia WGS

AF:

0.153

AC:

532

AN:

3478

EpiCase

AF:

0.227

EpiControl

AF:

0.229

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	This variant is associated with the following publications: (PMID: 32514006, 18759275, 30315176, 29958533, 28508493, 18834626) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hypouricemia, renal, 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jul 07, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	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

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.5

DANN

Benign

0.95

DEOGEN2

Benign

0.10

T;.;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.64

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.72

T;.;T

MetaRNN

Benign

0.028

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

0.90

P;P;P

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.47

N;N;N

REVEL

Benign

0.23

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.25

T;T;T

Polyphen

0.61

P;P;P

Vest4

0.078

MPC

0.18

ClinPred

0.0080

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.052

gMVP

0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over