rs2280205

Variant names:

• chr4-9908299-G-A
• rs2280205
• NM_020041.3:c.1049C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-9908299-G-A
• chr4-9908299-G-C
• chr4-9908299-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P350P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.38 (13735 hom., cov: 31)
  • Exomes 𝑓: 0.50 (186242 hom.)
• Consequence: SLC2A9 NM_020041.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.742
• Publications: 62 publications found

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 Gene-Disease associations (from GenCC):

• hypouricemia, renal, 2

  Inheritance: AD, AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary renal hypouricemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 350207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
SLC2A9	NM_020041.3	c.1049C>T	p.Pro350Leu	missense_variant	Exon 8 of 12	ENST00000264784.8	NP_064425.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A9	ENST00000264784.8	c.1049C>T	p.Pro350Leu	missense_variant	Exon 8 of 12	1	NM_020041.3	ENSP00000264784.3

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57795 AN: 151858 Hom.: 13725 Cov.: 31

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

GnomAD2 exomes AF: 0.442 AC: 111078 AN: 251316 AF XY: 0.452

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 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.: 41 AF XY: 0.497 AC XY: 361048 AN XY: 726644

African (AFR) AF: 0.0812 AC: 2719 AN: 33466

American (AMR) AF: 0.392 AC: 17527 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 14486 AN: 26116

East Asian (EAS) AF: 0.284 AC: 11268 AN: 39694

South Asian (SAS) AF: 0.422 AC: 36426 AN: 86222

European-Finnish (FIN) AF: 0.541 AC: 28914 AN: 53414

Middle Eastern (MID) AF: 0.460 AC: 2654 AN: 5764

European-Non Finnish (NFE) AF: 0.526 AC: 584704 AN: 1110708

Other (OTH) AF: 0.462 AC: 27853 AN: 60350

GnomAD4 genome AF: 0.380 AC: 57814 AN: 151976 Hom.: 13735 Cov.: 31 AF XY: 0.381 AC XY: 28317 AN XY: 74256

African (AFR) AF: 0.0986 AC: 4089 AN: 41490

American (AMR) AF: 0.412 AC: 6296 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1920 AN: 3470

East Asian (EAS) AF: 0.237 AC: 1226 AN: 5164

South Asian (SAS) AF: 0.412 AC: 1983 AN: 4812

European-Finnish (FIN) AF: 0.532 AC: 5598 AN: 10528

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35256 AN: 67932

Other (OTH) AF: 0.387 AC: 816 AN: 2106

Alfa AF: 0.469 Hom.: 70302

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

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30315176) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypouricemia, renal, 2 Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.68
DEOGEN2	Benign	0.17	T;.;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.76	T;.;T
MetaRNN	Benign	0.00012	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.94	L;.;.
PhyloP100		-0.74
PrimateAI	Benign	0.28	T
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	T
GERP RS		0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.58
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2280205; hg19: chr4-9909923; COSMIC: COSV53321281;