rs2280205

Positions:

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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

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=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 id is 350207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-9908299-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.514 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.1049C>T	p.Pro350Leu	missense_variant	8/12	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.1049C>T	p.Pro350Leu	missense_variant	8/12	1	NM_020041.3	ENSP00000264784	A2	Q9NRM0-1

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

GnomAD3 exomes

AF:

0.442

AC:

111078

AN:

251316

Hom.:

26773

AF XY:

0.452

AC XY:

61334

AN XY:

135824

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 SAS exome

AF:

0.418

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

Gnomad4 AFR exome

AF:

0.0812

Gnomad4 AMR exome

AF:

0.392

Gnomad4 ASJ exome

AF:

0.555

Gnomad4 EAS exome

AF:

0.284

Gnomad4 SAS exome

AF:

0.422

Gnomad4 FIN exome

AF:

0.541

Gnomad4 NFE exome

AF:

0.526

Gnomad4 OTH exome

AF:

0.462

GnomAD4 genome

AF:

0.380

AC:

57814

AN:

151976

Hom.:

13735

Cov.:

AF XY:

0.381

AC XY:

28317

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.0986

Gnomad4 AMR

AF:

0.412

Gnomad4 ASJ

AF:

0.553

Gnomad4 EAS

AF:

0.237

Gnomad4 SAS

AF:

0.412

Gnomad4 FIN

AF:

0.532

Gnomad4 NFE

AF:

0.519

Gnomad4 OTH

AF:

0.387

Alfa

AF:

0.491

Hom.:

49098

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

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

Hypouricemia, renal, 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.17

T;.;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.76

T;.;T

MetaRNN

Benign

0.00012

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.94

L;.;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.34

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.064

B;B;B

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

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

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