3-171009950-T-TGTGTGTGTGTGTGTGTGA

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000340.2(SLC2A2):​c.496+7_496+8insTCACACACACACACACAC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC2A2 NM_000340.2 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 3-171009950-T-TGTGTGTGTGTGTGTGTGA is Benign according to our data. Variant chr3-171009950-T-TGTGTGTGTGTGTGTGTGA is described in ClinVar as Likely_benign. ClinVar VariationId is 2031083.Status of the report is criteria_provided_single_submitter, 1 stars.

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+8insTCACACACACACACACAC		splice_region intron	N/A	NP_000331.1
	SLC2A2	NM_001278658.2		c.139+7_139+8insTCACACACACACACACAC		splice_region intron	N/A	NP_001265587.1
	SLC2A2	NM_001278659.2		c.-23-2688_-23-2687insTCACACACACACACACAC		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+8insTCACACACACACACACAC		splice_region intron	N/A	ENSP00000323568.3
	SLC2A2	ENST00000497642.5	TSL:1	n.372-2688_372-2687insTCACACACACACACACAC		intron	N/A	ENSP00000418456.1
	SLC2A2	ENST00000461867.1	TSL:3	c.-23-2688_-23-2687insTCACACACACACACACAC		intron	N/A	ENSP00000418888.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Fanconi-Bickel syndrome Benign:1

Sep 19, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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;