3-171009950-T-TGTGTGTGTGTGTGTGA

Variant names:

• chr3-171009950-T-TGTGTGTGTGTGTGTGA
• rs746295534
• NM_000340.2:c.496+7_496+8insTCACACACACACACAC

Variant summary

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

The NM_000340.2(SLC2A2):​c.496+7_496+8insTCACACACACACACAC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 150,744 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 32)
• Consequence: SLC2A2 NM_000340.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189
• Publications: 0 publications found

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]

SLC2A2 Gene-Disease associations (from GenCC):

• glycogen storage disease due to GLUT2 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, G2P
• neonatal diabetes mellitus

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• permanent neonatal diabetes mellitus

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• transient neonatal diabetes mellitus

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp

ENSG00000286856 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000340.2. 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
	SLC2A2	NM_000340.2	MANE Select	c.496+7_496+8insTCACACACACACACAC		splice_region intron	N/A	NP_000331.1
	SLC2A2	NM_001278658.2		c.139+7_139+8insTCACACACACACACAC		splice_region intron	N/A	NP_001265587.1
	SLC2A2	NM_001278659.2		c.-23-2688_-23-2687insTCACACACACACACAC		intron	N/A	NP_001265588.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A2	ENST00000314251.8	TSL:1 MANE Select	c.496+7_496+8insTCACACACACACACAC		splice_region intron	N/A	ENSP00000323568.3
	SLC2A2	ENST00000497642.5	TSL:1	n.372-2688_372-2687insTCACACACACACACAC		intron	N/A	ENSP00000418456.1
	SLC2A2	ENST00000461867.1	TSL:3	c.-23-2688_-23-2687insTCACACACACACACAC		intron	N/A	ENSP00000418888.1

Frequencies

GnomAD3 genomes AF: 0.0000199 AC: 3 AN: 150744 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000735

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 37

GnomAD4 genome AF: 0.0000199 AC: 3 AN: 150744 Hom.: 0 Cov.: 32 AF XY: 0.0000272 AC XY: 2 AN XY: 73498

African (AFR) AF: 0.0000735 AC: 3 AN: 40796

American (AMR) AF: 0.00 AC: 0 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67722

Other (OTH) AF: 0.00 AC: 0 AN: 2056

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.19

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs746295534; hg19: chr3-170727739;