4-9946940-T-C

Variant names:

• chr4-9946940-T-C
• rs998676
• NM_020041.3:c.682-4895A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020041.3(SLC2A9):​c.682-4895A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,038 control chromosomes in the GnomAD database, including 26,231 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (26231 hom., cov: 32)
• Consequence: SLC2A9 NM_020041.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 7 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: AR, AD, SD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• hereditary renal hypouricemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 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.682-4895A>G		intron	N/A	NP_064425.2
	SLC2A9	NM_001001290.2		c.595-4895A>G		intron	N/A	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.682-4895A>G		intron	N/A	ENSP00000264784.3	Q9NRM0-1
	SLC2A9	ENST00000309065.7	TSL:1	c.595-4895A>G		intron	N/A	ENSP00000311383.3	Q9NRM0-2
	SLC2A9	ENST00000505104.5	TSL:1	n.716-4895A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87105 AN: 151918 Hom.: 26178 Cov.: 32

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.557

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.574 AC: 87210 AN: 152038 Hom.: 26231 Cov.: 32 AF XY: 0.573 AC XY: 42600 AN XY: 74318

African (AFR) AF: 0.765 AC: 31736 AN: 41468

American (AMR) AF: 0.601 AC: 9185 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1712 AN: 3472

East Asian (EAS) AF: 0.569 AC: 2939 AN: 5168

South Asian (SAS) AF: 0.488 AC: 2344 AN: 4808

European-Finnish (FIN) AF: 0.487 AC: 5151 AN: 10580

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32541 AN: 67954

Other (OTH) AF: 0.557 AC: 1174 AN: 2108

Alfa AF: 0.474 Hom.: 7939

Bravo AF: 0.589

Asia WGS AF: 0.533 AC: 1856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.67
PhyloP100		0.021
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: rs998676; hg19: chr4-9948564;