rs2276961

Positions:

• chr4-10021357-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.73G>A​(p.Gly25Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,613,966 control chromosomes in the GnomAD database, including 227,232 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (16328 hom., cov: 34)
  • Exomes 𝑓: 0.53 (210904 hom.)
• Consequence: SLC2A9 NM_020041.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.194

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=1.5187014E-5).
• BP6: Variant 4-10021357-C-T is Benign according to our data. Variant chr4-10021357-C-T is described in ClinVar as [Benign]. Clinvar id is 347006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-10021357-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A9	NM_020041.3	c.73G>A	p.Gly25Arg	missense_variant	1/12	ENST00000264784.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A9	ENST00000264784.8	c.73G>A	p.Gly25Arg	missense_variant	1/12	1	NM_020041.3	A2

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66971 AN: 152052 Hom.: 16319 Cov.: 34

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.457

GnomAD3 exomes AF: 0.515 AC: 129356 AN: 251402 Hom.: 34470 AF XY: 0.524 AC XY: 71144 AN XY: 135888

Gnomad AFR exome AF: 0.202

Gnomad AMR exome AF: 0.537

Gnomad ASJ exome AF: 0.517

Gnomad EAS exome AF: 0.424

Gnomad SAS exome AF: 0.601

Gnomad FIN exome AF: 0.531

Gnomad NFE exome AF: 0.540

Gnomad OTH exome AF: 0.518

GnomAD4 exome AF: 0.534 AC: 780055 AN: 1461796 Hom.: 210904 Cov.: 60 AF XY: 0.536 AC XY: 389939 AN XY: 727202

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.530

Gnomad4 ASJ exome AF: 0.517

Gnomad4 EAS exome AF: 0.448

Gnomad4 SAS exome AF: 0.597

Gnomad4 FIN exome AF: 0.534

Gnomad4 NFE exome AF: 0.544

Gnomad4 OTH exome AF: 0.508

GnomAD4 genome AF: 0.440 AC: 66989 AN: 152170 Hom.: 16328 Cov.: 34 AF XY: 0.442 AC XY: 32910 AN XY: 74382

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.457

Alfa AF: 0.513 Hom.: 18393

Bravo AF: 0.426

TwinsUK AF: 0.546 AC: 2024

ALSPAC AF: 0.551 AC: 2124

ESP6500AA AF: 0.216 AC: 952

ESP6500EA AF: 0.537 AC: 4618

ExAC AF: 0.510 AC: 61941

Asia WGS AF: 0.509 AC: 1767 AN: 3478

EpiCase AF: 0.542

EpiControl AF: 0.528

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	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 30315176) -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Hypouricemia, renal, 2 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
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	Benign	0.096
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.0
DANN	Benign	0.92
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.000015	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.075
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.013	B
Vest4		0.056
MutPred		0.20		Loss of glycosylation at P29 (P = 0.0224);
MPC		0.13
ClinPred		0.015	T
GERP RS		-0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.25

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

Other links and lift over

dbSNP: rs2276961; hg19: chr4-10022981; COSMIC: COSV53316288; COSMIC: COSV53316288;