chr4-9937345-T-C

Variant names:

• chr4-9937345-T-C
• rs4447863
• NM_020041.3:c.814+4568A>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.814+4568A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,012 control chromosomes in the GnomAD database, including 27,618 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 0.59 (27618 hom., cov: 31)
• Consequence: SLC2A9 NM_020041.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 18 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A9	NM_020041.3	MANE Select	c.814+4568A>G		intron	N/A	NP_064425.2
	SLC2A9	NM_001001290.2		c.727+4568A>G		intron	N/A	NP_001001290.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A9	ENST00000264784.8	TSL:1 MANE Select	c.814+4568A>G		intron	N/A	ENSP00000264784.3
	SLC2A9	ENST00000309065.7	TSL:1	c.727+4568A>G		intron	N/A	ENSP00000311383.3
	SLC2A9	ENST00000505104.5	TSL:1	n.848+4568A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89430 AN: 151892 Hom.: 27558 Cov.: 31

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.589 AC: 89546 AN: 152012 Hom.: 27618 Cov.: 31 AF XY: 0.588 AC XY: 43654 AN XY: 74300

African (AFR) AF: 0.788 AC: 32637 AN: 41432

American (AMR) AF: 0.618 AC: 9440 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1735 AN: 3466

East Asian (EAS) AF: 0.570 AC: 2940 AN: 5160

South Asian (SAS) AF: 0.494 AC: 2375 AN: 4812

European-Finnish (FIN) AF: 0.490 AC: 5181 AN: 10570

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33565 AN: 67980

Other (OTH) AF: 0.574 AC: 1213 AN: 2112

Alfa AF: 0.525 Hom.: 36104

Bravo AF: 0.607

Asia WGS AF: 0.533 AC: 1859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.30
DANN	Benign	0.19
PhyloP100		-2.5
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: rs4447863; hg19: chr4-9938969;