chr4-9980681-G-C

Variant names:

• chr4-9980681-G-C
• rs121908322
• NM_020041.3:c.592C>G

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM2 PM5 PP3_Strong

The NM_020041.3(SLC2A9):​c.592C>G​(p.Arg198Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R198C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC2A9 NM_020041.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.96
• Publications: 0 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: Likely_pathogenic. The variant received 8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr4-9980680-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 1027407.Status of the report is no_assertion_criteria_provided, 0 stars.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.987

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.592C>G	p.Arg198Gly	missense	Exon 5 of 12	NP_064425.2
	SLC2A9	NM_001001290.2		c.505C>G	p.Arg169Gly	missense	Exon 6 of 13	NP_001001290.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A9	ENST00000264784.8	TSL:1 MANE Select	c.592C>G	p.Arg198Gly	missense	Exon 5 of 12	ENSP00000264784.3
	SLC2A9	ENST00000309065.7	TSL:1	c.505C>G	p.Arg169Gly	missense	Exon 6 of 13	ENSP00000311383.3
	SLC2A9	ENST00000505104.5	TSL:1	n.626C>G		non_coding_transcript_exon	Exon 6 of 12

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.70	D
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Pathogenic	0.90	D
MutationAssessor	Pathogenic	3.8	H
PhyloP100		5.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.99	D
Vest4		0.99
MutPred		0.97		Gain of glycosylation at S193 (P = 0.0561)
MVP		0.89
MPC		0.58
ClinPred		1.0	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.95
gMVP		0.93
Mutation Taster		=24/76	disease causing

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: rs121908322; hg19: chr4-9982305;