chr4-10019045-G-T

Position:

• chr4-10019045-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000264784.8(SLC2A9):​c.179C>A​(p.Ser60Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC2A9 ENST00000264784.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.78

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A9	NM_020041.3	c.179C>A	p.Ser60Tyr	missense_variant	2/12	ENST00000264784.8	NP_064425.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A9	ENST00000264784.8	c.179C>A	p.Ser60Tyr	missense_variant	2/12	1	NM_020041.3	ENSP00000264784	A2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2024

The c.179C>A (p.S60Y) alteration is located in exon 2 (coding exon 2) of the SLC2A9 gene. This alteration results from a C to A substitution at nucleotide position 179, causing the serine (S) at amino acid position 60 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;.;.;.
Eigen	Benign	0.035
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.86	D;.;D;D
M_CAP	Uncertain	0.27	D
MetaRNN	Uncertain	0.65	D;D;D;D
MetaSVM	Uncertain	0.013	D
MutationAssessor	Benign	1.6	L;.;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.5	N;N;N;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		0.98	D;P;P;.
Vest4		0.53
MutPred		0.64		Loss of sheet (P = 0.1158);.;.;.;
MVP		0.74
MPC		0.58
ClinPred		0.88	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-10020669;