4-9996869-A-G

Variant names:

• chr4-9996869-A-G
• rs13113918
• NM_020041.3:c.322T>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.322T>C​(p.Leu108Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 1,613,808 control chromosomes in the GnomAD database, including 509,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (47368 hom., cov: 33)
  • Exomes 𝑓: 0.79 (462151 hom.)
• Consequence: SLC2A9 NM_020041.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.96

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-AS1 (HGNC:40636): (SLC2A9 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 4-9996869-A-G is Benign according to our data. Variant chr4-9996869-A-G is described in ClinVar as [Benign]. Clinvar id is 350240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-9996869-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.96 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A9	NM_020041.3	c.322T>C	p.Leu108Leu	synonymous_variant	Exon 3 of 12	ENST00000264784.8	NP_064425.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A9	ENST00000264784.8	c.322T>C	p.Leu108Leu	synonymous_variant	Exon 3 of 12	1	NM_020041.3	ENSP00000264784.3

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119841 AN: 152120 Hom.: 47343 Cov.: 33

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.785

GnomAD3 exomes AF: 0.798 AC: 200740 AN: 251422 Hom.: 80579 AF XY: 0.797 AC XY: 108245 AN XY: 135876

Gnomad AFR exome AF: 0.772

Gnomad AMR exome AF: 0.769

Gnomad ASJ exome AF: 0.733

Gnomad EAS exome AF: 0.980

Gnomad SAS exome AF: 0.792

Gnomad FIN exome AF: 0.793

Gnomad NFE exome AF: 0.791

Gnomad OTH exome AF: 0.789

GnomAD4 exome AF: 0.794 AC: 1160636 AN: 1461570 Hom.: 462151 Cov.: 49 AF XY: 0.794 AC XY: 576996 AN XY: 727118

Gnomad4 AFR exome AF: 0.776

Gnomad4 AMR exome AF: 0.768

Gnomad4 ASJ exome AF: 0.738

Gnomad4 EAS exome AF: 0.985

Gnomad4 SAS exome AF: 0.788

Gnomad4 FIN exome AF: 0.797

Gnomad4 NFE exome AF: 0.791

Gnomad4 OTH exome AF: 0.794

GnomAD4 genome AF: 0.788 AC: 119918 AN: 152238 Hom.: 47368 Cov.: 33 AF XY: 0.788 AC XY: 58653 AN XY: 74424

Gnomad4 AFR AF: 0.777

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.790

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.790

Gnomad4 OTH AF: 0.787

Alfa AF: 0.785 Hom.: 60060

Bravo AF: 0.786

Asia WGS AF: 0.883 AC: 3069 AN: 3478

EpiCase AF: 0.784

EpiControl AF: 0.779

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

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
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.81

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: rs13113918; hg19: chr4-9998493;