4-9980265-T-C

Variant names:

• chr4-9980265-T-C
• rs13131257
• NM_020041.3:c.681+327A>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.681+327A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,106 control chromosomes in the GnomAD database, including 39,578 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 0.71 (39578 hom., cov: 33)
• Consequence: SLC2A9 NM_020041.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A9	NM_020041.3	c.681+327A>G		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.681+327A>G		intron_variant	Intron 5 of 11	1	NM_020041.3	ENSP00000264784.3
SLC2A9	ENST00000309065.7	c.594+327A>G		intron_variant	Intron 6 of 12	1		ENSP00000311383.3
SLC2A9	ENST00000505104.5	n.715+327A>G		intron_variant	Intron 6 of 11	1
SLC2A9	ENST00000506583.5	c.594+327A>G		intron_variant	Intron 7 of 13	5		ENSP00000422209.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107779 AN: 151988 Hom.: 39570 Cov.: 33

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.709 AC: 107820 AN: 152106 Hom.: 39578 Cov.: 33 AF XY: 0.711 AC XY: 52896 AN XY: 74348

African (AFR) AF: 0.517 AC: 21420 AN: 41452

American (AMR) AF: 0.643 AC: 9826 AN: 15282

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

East Asian (EAS) AF: 0.981 AC: 5088 AN: 5184

South Asian (SAS) AF: 0.774 AC: 3729 AN: 4818

European-Finnish (FIN) AF: 0.827 AC: 8739 AN: 10572

Middle Eastern (MID) AF: 0.771 AC: 225 AN: 292

European-Non Finnish (NFE) AF: 0.793 AC: 53921 AN: 68012

Other (OTH) AF: 0.731 AC: 1545 AN: 2114

Alfa AF: 0.759 Hom.: 20623

Bravo AF: 0.688

Asia WGS AF: 0.839 AC: 2919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.74
DANN	Benign	0.70
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: rs13131257; hg19: chr4-9981889;