rs121908323

chr4-9887623-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PP3_Moderate PP5

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
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.40

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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/exons	MANE	UniProt
SLC2A9	NM_020041.3	c.1235C>G	p.Pro412Arg	missense_variant	10/12	ENST00000264784.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A9	ENST00000264784.8	c.1235C>G	p.Pro412Arg	missense_variant	10/12	1	NM_020041.3	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000575 AC: 1 AN: 173986 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 92120

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000285 AC: 40 AN: 1403960 Hom.: 0 Cov.: 31 AF XY: 0.0000274 AC XY: 19 AN XY: 692382

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00109

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000835 AC: 1

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hypouricemia, renal, 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 03, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
Cadd	Benign	21
Dann	Benign	0.97
DEOGEN2	Benign	0.38	T;.;.
Eigen	Benign	-0.0076
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.73	T;.;T
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.92	D;D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.9	L;.;.
MutationTaster	Benign	0.96	A;A;A
PrimateAI	Benign	0.45	T
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	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.52
gMVP		0.91

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

LitVar

Other links and lift over

dbSNP: rs121908323; hg19: chr4-9889247;