4-9980706-A-G

Variant names:

• chr4-9980706-A-G
• rs13125646
• NM_020041.3:c.567T>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020041.3(SLC2A9):​c.567T>C​(p.Leu189Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 1,613,922 control chromosomes in the GnomAD database, including 497,654 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (41623 hom., cov: 32)
  • Exomes 𝑓: 0.79 (456031 hom.)
• Consequence: SLC2A9 NM_020041.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0220

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 4-9980706-A-G is Benign according to our data. Variant chr4-9980706-A-G is described in ClinVar as [Benign]. Clinvar id is 350235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-9980706-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.022 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A9	NM_020041.3	c.567T>C	p.Leu189Leu	synonymous_variant	Exon 5 of 12	ENST00000264784.8	NP_064425.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A9	ENST00000264784.8	c.567T>C	p.Leu189Leu	synonymous_variant	Exon 5 of 12	1	NM_020041.3	ENSP00000264784.3

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111434 AN: 151980 Hom.: 41600 Cov.: 32

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.858

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.745

GnomAD3 exomes AF: 0.766 AC: 191718 AN: 250416 Hom.: 74745 AF XY: 0.772 AC XY: 104438 AN XY: 135340

Gnomad AFR exome AF: 0.589

Gnomad AMR exome AF: 0.609

Gnomad ASJ exome AF: 0.741

Gnomad EAS exome AF: 0.984

Gnomad SAS exome AF: 0.762

Gnomad FIN exome AF: 0.828

Gnomad NFE exome AF: 0.794

Gnomad OTH exome AF: 0.772

GnomAD4 exome AF: 0.787 AC: 1151063 AN: 1461824 Hom.: 456031 Cov.: 63 AF XY: 0.788 AC XY: 572692 AN XY: 727216

Gnomad4 AFR exome AF: 0.593

Gnomad4 AMR exome AF: 0.616

Gnomad4 ASJ exome AF: 0.746

Gnomad4 EAS exome AF: 0.988

Gnomad4 SAS exome AF: 0.761

Gnomad4 FIN exome AF: 0.832

Gnomad4 NFE exome AF: 0.794

Gnomad4 OTH exome AF: 0.782

GnomAD4 genome AF: 0.733 AC: 111503 AN: 152098 Hom.: 41623 Cov.: 32 AF XY: 0.735 AC XY: 54624 AN XY: 74346

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.981

Gnomad4 SAS AF: 0.773

Gnomad4 FIN AF: 0.827

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.748

Alfa AF: 0.768 Hom.: 47955

Bravo AF: 0.715

Asia WGS AF: 0.852 AC: 2961 AN: 3478

EpiCase AF: 0.784

EpiControl AF: 0.780

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hypouricemia, renal, 2 Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	3.8
DANN	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

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: rs13125646; hg19: chr4-9982330;