rs73225891

Positions:

chr4-9920546-C-G

Variant summary

Our verdict is Benign. Variant got -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:3

Conservation

PhyloP100: 3.62

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=0.020402223).

BP6

Variant 4-9920546-C-G is Benign according to our data. Variant chr4-9920546-C-G is described in ClinVar as [Benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 53 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A9	NM_020041.3 linkuse as main transcript	c.841G>C	p.Asp281His	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.841G>C	p.Asp281His	missense_variant	7/12	1	NM_020041.3	A2	Q9NRM0-1
SLC2A9	ENST00000309065.7 linkuse as main transcript	c.754G>C	p.Asp252His	missense_variant	8/13	1		P2	Q9NRM0-2
SLC2A9	ENST00000505104.5 linkuse as main transcript	n.875G>C		non_coding_transcript_exon_variant	8/12	1
SLC2A9	ENST00000506583.5 linkuse as main transcript	c.754G>C	p.Asp252His	missense_variant	9/14	5		P2	Q9NRM0-2

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

GnomAD3 exomes

AF:

0.0198

AC:

4962

AN:

251194

Hom.:

AF XY:

0.0196

AC XY:

2669

AN XY:

135838

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 SAS exome

AF:

0.00258

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

Gnomad4 AFR exome

AF:

0.00409

Gnomad4 AMR exome

AF:

0.00566

Gnomad4 ASJ exome

AF:

0.0133

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00254

Gnomad4 FIN exome

AF:

0.0480

Gnomad4 NFE exome

AF:

0.0275

Gnomad4 OTH exome

AF:

0.0200

GnomAD4 genome

AF:

0.0187

AC:

2852

AN:

152314

Hom.:

Cov.:

AF XY:

0.0192

AC XY:

1432

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00390

Gnomad4 AMR

AF:

0.00817

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0522

Gnomad4 NFE

AF:

0.0280

Gnomad4 OTH

AF:

0.0180

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

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	GeneDx	Feb 13, 2020	This variant is associated with the following publications: (PMID: 25268603, 30315176) -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 22, 2024	- -

Hypouricemia, renal, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

T;.;.

Eigen

Uncertain

0.35

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;.;D

MetaRNN

Benign

0.020

T;T;T

MetaSVM

Uncertain

0.19

MutationAssessor

Pathogenic

3.3

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-4.7

D;D;D

REVEL

Uncertain

0.43

Sift

Benign

0.031

D;D;D

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.66

MPC

0.56

ClinPred

0.019

GERP RS

4.3

Varity_R

0.65

gMVP

0.70

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