Genetic Variant SLC2A9:p.Pro412Arg (chr4-9887623-G-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PP3_ModeratePP5

The NM_020041.3(SLC2A9):c.1235C>G(p.Pro412Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,403,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

SLC2A9
NM_020041.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.40

Publications

10 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.918

PP5

Variant 4-9887623-G-C is Pathogenic according to our data. Variant chr4-9887623-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 4598.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A9	NM_020041.3 link	c.1235C>G	p.Pro412Arg	missense_variant	Exon 10 of 12	ENST00000264784.8	NP_064425.2	Q9NRM0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A9	ENST00000264784.8 link	c.1235C>G	p.Pro412Arg	missense_variant	Exon 10 of 12	1	NM_020041.3	ENSP00000264784.3		Q9NRM0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000575

AC:

AN:

173986

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000763

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000285

AC:

AN:

1403960

Hom.:

Cov.:

AF XY:

0.0000274

AC XY:

AN XY:

692382

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32038

American (AMR)

AF:

0.00

AC:

AN:

38348

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24156

East Asian (EAS)

AF:

0.00109

AC:

AN:

36682

South Asian (SAS)

AF:

0.00

AC:

AN:

77268

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50474

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5620

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1081384

Other (OTH)

AF:

0.00

AC:

AN:

57990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000835

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hypouricemia, renal, 2

Pathogenic:1

Oct 03, 2008

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.38

T;.;.

Eigen

Benign

-0.0076

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.73

T;.;T

M_CAP

Benign

0.021

MetaRNN

Pathogenic

0.92

D;D;D

MetaSVM

Benign

-0.40

MutationAssessor

Benign

1.9

L;.;.

PhyloP100

3.4

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-4.5

D;D;D

REVEL

Uncertain

0.32

Sift

Benign

0.27

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.024

B;B;B

Vest4

0.84

MutPred

0.88

Loss of helix (P = 0.1706);.;.;

MVP

0.71

MPC

0.35

ClinPred

0.61

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.52

gMVP

0.91

Mutation Taster

=12/88

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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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4-9887623-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over