rs16890979

chr4-9920543-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.76

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]

ACMG classification

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	UniProt
SLC2A9	NM_020041.3	c.844G>A	p.Val282Ile	missense_variant	7/12	ENST00000264784.8

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42936 AN: 152072 Hom.: 6956 Cov.: 33

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

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.: 38 AF XY: 0.223 AC XY: 162344 AN XY: 727190

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.: 33 AF XY: 0.279 AC XY: 20794 AN XY: 74404

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:4

Revision: criteria provided, multiple submitters, no conflicts

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	Aug 20, 2019	This variant is associated with the following publications: (PMID: 32514006, 18759275, 30315176, 29958533, 28508493, 18834626) -

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	T
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	D
LIST_S2	Benign	0.72	T;.;T
MetaRNN	Benign	0.028	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M;.;.
MutationTaster	Benign	0.90	P;P;P
PrimateAI	Benign	0.30	T
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	T
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

Other links and lift over

dbSNP: rs16890979; hg19: chr4-9922167; COSMIC: COSV53316809; COSMIC: COSV53316809;