4-9980706-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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 (★★). Synonymous variant affecting the same amino acid position (i.e. L189L) has been classified as Likely 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
• Publications: 33 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hereditary renal hypouricemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 350235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020041.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A9	NM_020041.3	MANE Select	c.567T>C	p.Leu189Leu	synonymous	Exon 5 of 12	NP_064425.2
	SLC2A9	NM_001001290.2		c.480T>C	p.Leu160Leu	synonymous	Exon 6 of 13	NP_001001290.1	Q9NRM0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A9	ENST00000264784.8	TSL:1 MANE Select	c.567T>C	p.Leu189Leu	synonymous	Exon 5 of 12	ENSP00000264784.3	Q9NRM0-1
	SLC2A9	ENST00000309065.7	TSL:1	c.480T>C	p.Leu160Leu	synonymous	Exon 6 of 13	ENSP00000311383.3	Q9NRM0-2
	SLC2A9	ENST00000505104.5	TSL:1	n.601T>C		non_coding_transcript_exon	Exon 6 of 12

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

GnomAD2 exomes AF: 0.766 AC: 191718 AN: 250416 AF XY: 0.772

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 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

African (AFR) AF: 0.593 AC: 19836 AN: 33478

American (AMR) AF: 0.616 AC: 27541 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 19493 AN: 26136

East Asian (EAS) AF: 0.988 AC: 39229 AN: 39698

South Asian (SAS) AF: 0.761 AC: 65673 AN: 86254

European-Finnish (FIN) AF: 0.832 AC: 44448 AN: 53412

Middle Eastern (MID) AF: 0.756 AC: 4361 AN: 5768

European-Non Finnish (NFE) AF: 0.794 AC: 883255 AN: 1111968

Other (OTH) AF: 0.782 AC: 47227 AN: 60390

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

African (AFR) AF: 0.601 AC: 24916 AN: 41456

American (AMR) AF: 0.653 AC: 9986 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2544 AN: 3468

East Asian (EAS) AF: 0.981 AC: 5064 AN: 5160

South Asian (SAS) AF: 0.773 AC: 3727 AN: 4820

European-Finnish (FIN) AF: 0.827 AC: 8753 AN: 10586

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.793 AC: 53922 AN: 67996

Other (OTH) AF: 0.748 AC: 1583 AN: 2116

Alfa AF: 0.767 Hom.: 129927

Bravo AF: 0.715

Asia WGS AF: 0.852 AC: 2961 AN: 3478

EpiCase AF: 0.784

EpiControl AF: 0.780

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Hypouricemia, renal, 2 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	3.8
DANN	Benign	0.42
PhyloP100		-0.022
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13125646; hg19: chr4-9982330; COSMIC: COSV108066859; COSMIC: COSV108066859;