NM_020041.3:c.1049C>A

Variant names:

• chr4-9908299-G-T
• rs2280205
• NM_020041.3:c.1049C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020041.3(SLC2A9):​c.1049C>A​(p.Pro350Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign 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. P350L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC2A9 NM_020041.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.742
• Publications: 62 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.070067376).

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.1049C>A	p.Pro350Gln	missense	Exon 8 of 12	NP_064425.2
	SLC2A9	NM_001001290.2		c.962C>A	p.Pro321Gln	missense	Exon 9 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.1049C>A	p.Pro350Gln	missense	Exon 8 of 12	ENSP00000264784.3
	SLC2A9	ENST00000309065.7	TSL:1	c.962C>A	p.Pro321Gln	missense	Exon 9 of 13	ENSP00000311383.3
	SLC2A9	ENST00000505104.5	TSL:1	n.1083C>A		non_coding_transcript_exon	Exon 9 of 12

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 70302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	5.0
DANN	Benign	0.28
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-0.12	N
PhyloP100		-0.74
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.16
Sift	Benign	0.63	T
Sift4G	Benign	0.58	T
Polyphen		0.030	B
Vest4		0.16
MutPred		0.45		Loss of catalytic residue at P349 (P = 0.0231)
MVP		0.43
MPC		0.11
ClinPred		0.16	T
GERP RS		0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.099
gMVP		0.39
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs2280205; hg19: chr4-9909923;