chr4-9942428-A-G

Variant names:

• chr4-9942428-A-G
• rs12498742
• NM_020041.3:c.682-383T>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.682-383T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,074 control chromosomes in the GnomAD database, including 9,342 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 0.32 (9342 hom., cov: 32)
• Consequence: SLC2A9 NM_020041.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 41 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A9	NM_020041.3	c.682-383T>C		intron_variant	Intron 5 of 11	ENST00000264784.8	NP_064425.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A9	ENST00000264784.8	c.682-383T>C		intron_variant	Intron 5 of 11	1	NM_020041.3	ENSP00000264784.3
SLC2A9	ENST00000309065.7	c.595-383T>C		intron_variant	Intron 6 of 12	1		ENSP00000311383.3
SLC2A9	ENST00000505104.5	n.716-383T>C		intron_variant	Intron 6 of 11	1
SLC2A9	ENST00000506583.5	c.595-383T>C		intron_variant	Intron 7 of 13	5		ENSP00000422209.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48818 AN: 151956 Hom.: 9309 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.0199

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.322 AC: 48908 AN: 152074 Hom.: 9342 Cov.: 32 AF XY: 0.320 AC XY: 23766 AN XY: 74354

African (AFR) AF: 0.521 AC: 21615 AN: 41482

American (AMR) AF: 0.384 AC: 5875 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 999 AN: 3468

East Asian (EAS) AF: 0.0201 AC: 104 AN: 5172

South Asian (SAS) AF: 0.257 AC: 1239 AN: 4816

European-Finnish (FIN) AF: 0.216 AC: 2289 AN: 10592

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15910 AN: 67954

Other (OTH) AF: 0.296 AC: 624 AN: 2108

Alfa AF: 0.292 Hom.: 3144

Bravo AF: 0.340

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.2
DANN	Benign	0.79
PhyloP100		1.2
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: rs12498742; hg19: chr4-9944052;