4-9920506-C-T

Position:

chr4-9920506-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.881G>A(p.Arg294His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,614,018 control chromosomes in the GnomAD database, including 43,797 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3490 hom., cov: 33)

Exomes 𝑓: 0.21 ( 40307 hom. )

Consequence

SLC2A9
NM_020041.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0290

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=7.065905E-6).

BP6

Variant 4-9920506-C-T is Benign according to our data. Variant chr4-9920506-C-T is described in ClinVar as [Benign]. Clinvar id is 350213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-9920506-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A9	NM_020041.3 linkuse as main transcript	c.881G>A	p.Arg294His	missense_variant	7/12	ENST00000264784.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A9	ENST00000264784.8 linkuse as main transcript	c.881G>A	p.Arg294His	missense_variant	7/12	1	NM_020041.3	A2	Q9NRM0-1
SLC2A9	ENST00000309065.7 linkuse as main transcript	c.794G>A	p.Arg265His	missense_variant	8/13	1		P2	Q9NRM0-2
SLC2A9	ENST00000505104.5 linkuse as main transcript	n.915G>A		non_coding_transcript_exon_variant	8/12	1
SLC2A9	ENST00000506583.5 linkuse as main transcript	c.794G>A	p.Arg265His	missense_variant	9/14	5		P2	Q9NRM0-2

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27517

AN:

152118

Hom.:

3490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0689

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.147

Gnomad EAS

AF:

0.663

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.178

GnomAD3 exomes

AF:

0.246

AC:

61854

AN:

251088

Hom.:

10057

AF XY:

0.252

AC XY:

34228

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.0668

Gnomad AMR exome

AF:

0.223

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.671

Gnomad SAS exome

AF:

0.363

Gnomad FIN exome

AF:

0.240

Gnomad NFE exome

AF:

0.189

Gnomad OTH exome

AF:

0.221

GnomAD4 exome

AF:

0.214

AC:

313476

AN:

1461782

Hom.:

40307

Cov.:

AF XY:

0.219

AC XY:

159222

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.0624

Gnomad4 AMR exome

AF:

0.223

Gnomad4 ASJ exome

AF:

0.162

Gnomad4 EAS exome

AF:

0.691

Gnomad4 SAS exome

AF:

0.361

Gnomad4 FIN exome

AF:

0.240

Gnomad4 NFE exome

AF:

0.190

Gnomad4 OTH exome

AF:

0.215

GnomAD4 genome

AF:

0.181

AC:

27522

AN:

152236

Hom.:

3490

Cov.:

AF XY:

0.190

AC XY:

14133

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0688

Gnomad4 AMR

AF:

0.194

Gnomad4 ASJ

AF:

0.147

Gnomad4 EAS

AF:

0.662

Gnomad4 SAS

AF:

0.380

Gnomad4 FIN

AF:

0.243

Gnomad4 NFE

AF:

0.188

Gnomad4 OTH

AF:

0.181

Alfa

AF:

0.196

Hom.:

8757

Bravo

AF:

0.171

TwinsUK

AF:

0.201

AC:

746

ALSPAC

AF:

0.186

AC:

717

ESP6500AA

AF:

0.0713

AC:

314

ESP6500EA

AF:

0.189

AC:

1629

ExAC

AF:

0.245

AC:

29794

Asia WGS

AF:

0.454

AC:

1573

AN:

3478

EpiCase

AF:

0.188

EpiControl

AF:

0.182

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 19723617, 21658257) -

Hypouricemia, renal, 2

Benign:1

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

0.092

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

T;.;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.77

T;.;T

MetaRNN

Benign

0.0000071

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.013

D;D;D

Sift4G

Uncertain

0.023

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.094

MPC

0.14

ClinPred

0.022

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.43

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

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