Genetic Variant NM_020041.3:c.592C>G (chr4-9980681-G-C) – ACMG Classification: Likely_pathogenic (8 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM2PM5PP3_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.96

Publications

0 publications found

Variant links:

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

SLC2A9 links:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
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.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

BayesDel_noAF

Pathogenic

0.35

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.70

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.99

MetaSVM

Pathogenic

0.90

MutationAssessor

Pathogenic

3.8

PhyloP100

5.0

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-6.5

REVEL

Pathogenic

0.82

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

0.99

Vest4

0.99

MutPred

0.97

Gain of glycosylation at S193 (P = 0.0561)

MVP

0.89

MPC

0.58

ClinPred

1.0

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

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over