chr4-9866969-A-T

Variant names:

• chr4-9866969-A-T
• rs939134
• NM_020041.3:c.1291+20598T>A

Variant summary

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

The NM_020041.3(SLC2A9):​c.1291+20598T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,970 control chromosomes in the GnomAD database, including 10,871 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 0.35 (10871 hom., cov: 32)
• Consequence: SLC2A9 NM_020041.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 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.1291+20598T>A		intron	N/A	NP_064425.2
	SLC2A9	NM_001001290.2		c.1204+20598T>A		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.1291+20598T>A		intron	N/A	ENSP00000264784.3	Q9NRM0-1
	SLC2A9	ENST00000309065.7	TSL:1	c.1204+20598T>A		intron	N/A	ENSP00000311383.3	Q9NRM0-2
	SLC2A9	ENST00000851832.1		c.1237+20598T>A		intron	N/A	ENSP00000521891.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52698 AN: 151852 Hom.: 10850 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.347 AC: 52767 AN: 151970 Hom.: 10871 Cov.: 32 AF XY: 0.348 AC XY: 25832 AN XY: 74296

African (AFR) AF: 0.558 AC: 23131 AN: 41426

American (AMR) AF: 0.433 AC: 6605 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 851 AN: 3472

East Asian (EAS) AF: 0.397 AC: 2044 AN: 5152

South Asian (SAS) AF: 0.308 AC: 1485 AN: 4816

European-Finnish (FIN) AF: 0.196 AC: 2074 AN: 10572

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15534 AN: 67966

Other (OTH) AF: 0.325 AC: 686 AN: 2110

Alfa AF: 0.295 Hom.: 1013

Bravo AF: 0.374

Asia WGS AF: 0.348 AC: 1212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.45
DANN	Benign	0.63
PhyloP100		-1.5
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: rs939134; hg19: chr4-9868593;