3-170997894-GTT-GTTTT

Variant names:

• chr3-170997894-G-GTT
• rs573575421
• NM_000340.2:c.*7_*8dupAA

Variant summary

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

The NM_000340.2(SLC2A2):​c.*7_*8dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,432,256 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000074 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: SLC2A2 NM_000340.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.929
• 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: PanelApp Australia, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A2	NM_000340.2	MANE Select	c.*7_*8dupAA		3_prime_UTR	Exon 11 of 11	NP_000331.1	P11168-1
	SLC2A2	NM_001278658.2		c.*7_*8dupAA		3_prime_UTR	Exon 10 of 10	NP_001265587.1	P11168-2
	SLC2A2	NM_001278659.2		c.*7_*8dupAA		3_prime_UTR	Exon 10 of 10	NP_001265588.1	Q6PAU8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A2	ENST00000314251.8	TSL:1 MANE Select	c.*7_*8dupAA		3_prime_UTR	Exon 11 of 11	ENSP00000323568.3	P11168-1
	SLC2A2	ENST00000497642.5	TSL:1	n.*1049_*1050dupAA		non_coding_transcript_exon	Exon 10 of 10	ENSP00000418456.1	A0A0C4DH64
	SLC2A2	ENST00000497642.5	TSL:1	n.*1049_*1050dupAA		3_prime_UTR	Exon 10 of 10	ENSP00000418456.1	A0A0C4DH64

Frequencies

GnomAD3 genomes AF: 0.0000743 AC: 11 AN: 148030 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000745

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: 0.000120

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000778 AC: 13 AN: 167030 AF XY: 0.0000764

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000476

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000254

GnomAD4 exome AF: 0.000135 AC: 174 AN: 1284226 Hom.: 0 Cov.: 30 AF XY: 0.000124 AC XY: 79 AN XY: 639494

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000680 AC: 2 AN: 29394

American (AMR) AF: 0.0000251 AC: 1 AN: 39814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22886

East Asian (EAS) AF: 0.00 AC: 0 AN: 35322

South Asian (SAS) AF: 0.0000797 AC: 6 AN: 75328

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5238

European-Non Finnish (NFE) AF: 0.000167 AC: 163 AN: 975642

Other (OTH) AF: 0.0000377 AC: 2 AN: 53076

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000743 AC: 11 AN: 148030 Hom.: 0 Cov.: 32 AF XY: 0.0000832 AC XY: 6 AN XY: 72102

African (AFR) AF: 0.0000745 AC: 3 AN: 40244

American (AMR) AF: 0.00 AC: 0 AN: 14800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3412

East Asian (EAS) AF: 0.00 AC: 0 AN: 5104

South Asian (SAS) AF: 0.00 AC: 0 AN: 4652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.000120 AC: 8 AN: 66694

Other (OTH) AF: 0.00 AC: 0 AN: 2022

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Fanconi-Bickel syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.93

Splicing

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

Other links and lift over

dbSNP: rs573575421; hg19: chr3-170715683;