3-170999069-A-G

Position:

• chr3-170999069-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_000340.2(SLC2A2):​c.1166T>C​(p.Leu389Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SLC2A2 NM_000340.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.76

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 Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.978
• PP5: Variant 3-170999069-A-G is Pathogenic according to our data. Variant chr3-170999069-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 16104.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A2	NM_000340.2	c.1166T>C	p.Leu389Pro	missense_variant	9/11	ENST00000314251.8	NP_000331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A2	ENST00000314251.8	c.1166T>C	p.Leu389Pro	missense_variant	9/11	1	NM_000340.2	ENSP00000323568	P1
SLC2A2	ENST00000497642.5	c.*633T>C		3_prime_UTR_variant, NMD_transcript_variant	8/10	1		ENSP00000418456
	ENST00000655926.1	n.291+4044A>G		intron_variant, non_coding_transcript_variant
SLC2A2	ENST00000469787.1	c.*633T>C		3_prime_UTR_variant, NMD_transcript_variant	8/10	2		ENSP00000417918

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Fanconi-Bickel syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2000

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.82	D
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.099
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.68	D
MutationAssessor	Pathogenic	3.2	M
MutationTaster	Benign	0.98	A;A
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.84	P
Vest4		0.95
MutPred		0.83		Loss of ubiquitination at K392 (P = 0.0924);
MVP		0.93
MPC		0.80
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.92
gMVP		0.92

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: rs121909747; hg19: chr3-170716858;