NM_020041.3:c.681+16111A>C

Variant names:

• chr4-9964481-T-G
• rs6449173
• NM_020041.3:c.681+16111A>C

Variant summary

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

The NM_020041.3(SLC2A9):​c.681+16111A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,144 control chromosomes in the GnomAD database, including 6,439 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 0.27 (6439 hom., cov: 33)
• Consequence: SLC2A9 NM_020041.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.457
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 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.681+16111A>C		intron	N/A	NP_064425.2
	SLC2A9	NM_001001290.2		c.594+16111A>C		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.681+16111A>C		intron	N/A	ENSP00000264784.3	Q9NRM0-1
	SLC2A9	ENST00000309065.7	TSL:1	c.594+16111A>C		intron	N/A	ENSP00000311383.3	Q9NRM0-2
	SLC2A9	ENST00000505104.5	TSL:1	n.715+16111A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41746 AN: 152026 Hom.: 6427 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.275 AC: 41794 AN: 152144 Hom.: 6439 Cov.: 33 AF XY: 0.273 AC XY: 20322 AN XY: 74372

African (AFR) AF: 0.402 AC: 16699 AN: 41492

American (AMR) AF: 0.355 AC: 5423 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 943 AN: 3472

East Asian (EAS) AF: 0.0193 AC: 100 AN: 5182

South Asian (SAS) AF: 0.256 AC: 1232 AN: 4818

European-Finnish (FIN) AF: 0.184 AC: 1948 AN: 10602

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.216 AC: 14708 AN: 67988

Other (OTH) AF: 0.258 AC: 543 AN: 2104

Alfa AF: 0.268 Hom.: 1319

Bravo AF: 0.291

Asia WGS AF: 0.159 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.45
PhyloP100		0.46
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: rs6449173; hg19: chr4-9966105;