3-170998041-G-T

Position:

• chr3-170998041-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000340.2(SLC2A2):​c.1437C>A​(p.Phe479Leu) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F479F) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC2A2 NM_000340.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739

Genes affected

SLC2A2 (HGNC:11006): (solute carrier family 2 member 2) This gene encodes an integral plasma membrane glycoprotein of the liver, islet beta cells, intestine, and kidney epithelium. The encoded protein mediates facilitated bidirectional glucose transport. Because of its low affinity for glucose, it has been suggested as a glucose sensor. Mutations in this gene are associated with susceptibility to diseases, including Fanconi-Bickel syndrome and noninsulin-dependent diabetes mellitus (NIDDM). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.786

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A2	NM_000340.2	c.1437C>A	p.Phe479Leu	missense_variant	11/11	ENST00000314251.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A2	ENST00000314251.8	c.1437C>A	p.Phe479Leu	missense_variant	11/11	1	NM_000340.2	P1
SLC2A2	ENST00000497642.5	c.*904C>A		3_prime_UTR_variant, NMD_transcript_variant	10/10	1
	ENST00000655926.1	n.291+3016G>T		intron_variant, non_coding_transcript_variant
SLC2A2	ENST00000469787.1	c.*904C>A		3_prime_UTR_variant, NMD_transcript_variant	10/10	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250066 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135376

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461404 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 727008

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Uncertain	0.75	D
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.089	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	0.0020	P;P
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.37	B
Vest4		0.39
MutPred		0.63		Loss of ubiquitination at K483 (P = 0.2646);
MVP		0.55
MPC		0.23
ClinPred		0.88	D
GERP RS		-3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.70
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs5398; hg19: chr3-170715830;