4-9980420-A-C

Variant names:

• chr4-9980420-A-C
• rs13125209
• NM_020041.3:c.681+172T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020041.3(SLC2A9):​c.681+172T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,106 control chromosomes in the GnomAD database, including 40,338 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.72 (40338 hom., cov: 33)
• Consequence: SLC2A9 NM_020041.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.240
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 4-9980420-A-C is Benign according to our data. Variant chr4-9980420-A-C is described in ClinVar as Benign. ClinVar VariationId is 1295132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 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.681+172T>G		intron	N/A	NP_064425.2
	SLC2A9	NM_001001290.2		c.594+172T>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.681+172T>G		intron	N/A	ENSP00000264784.3
	SLC2A9	ENST00000309065.7	TSL:1	c.594+172T>G		intron	N/A	ENSP00000311383.3
	SLC2A9	ENST00000505104.5	TSL:1	n.715+172T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109234 AN: 151988 Hom.: 40331 Cov.: 33

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.718 AC: 109274 AN: 152106 Hom.: 40338 Cov.: 33 AF XY: 0.720 AC XY: 53577 AN XY: 74370

African (AFR) AF: 0.551 AC: 22830 AN: 41452

American (AMR) AF: 0.645 AC: 9864 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2546 AN: 3472

East Asian (EAS) AF: 0.981 AC: 5085 AN: 5182

South Asian (SAS) AF: 0.774 AC: 3733 AN: 4822

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

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.793 AC: 53908 AN: 67998

Other (OTH) AF: 0.738 AC: 1560 AN: 2114

Alfa AF: 0.760 Hom.: 9264

Bravo AF: 0.699

Asia WGS AF: 0.840 AC: 2921 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	9.5
DANN	Benign	0.80
PhyloP100		-0.24
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: rs13125209; hg19: chr4-9982044;