3-170996696-C-T

Variant names:

• chr3-170996696-C-T
• rs28579899
• NM_000340.2:c.*1207G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_000340.2(SLC2A2):​c.*1207G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000463 in 397,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (0 hom.)
• Consequence: SLC2A2 NM_000340.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0110
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000671 (102/152122) while in subpopulation AFR AF = 0.00186 (77/41500). AF 95% confidence interval is 0.00152. There are 0 homozygotes in GnomAd4. There are 56 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.*1207G>A		3_prime_UTR	Exon 11 of 11	NP_000331.1	P11168-1
	SLC2A2	NM_001278658.2		c.*1207G>A		3_prime_UTR	Exon 10 of 10	NP_001265587.1	P11168-2
	SLC2A2	NM_001278659.2		c.*1207G>A		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.*1207G>A		3_prime_UTR	Exon 11 of 11	ENSP00000323568.3	P11168-1
	SLC2A2	ENST00000878399.1		c.*1207G>A		3_prime_UTR	Exon 11 of 11	ENSP00000548458.1
	SLC2A2	ENST00000878398.1		c.*1207G>A		3_prime_UTR	Exon 10 of 10	ENSP00000548457.1

Frequencies

GnomAD3 genomes AF: 0.000671 AC: 102 AN: 152004 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000334 AC: 82 AN: 245530 Hom.: 0 Cov.: 0 AF XY: 0.000305 AC XY: 38 AN XY: 124436

African (AFR) AF: 0.00294 AC: 21 AN: 7144

American (AMR) AF: 0.00121 AC: 9 AN: 7420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9206

East Asian (EAS) AF: 0.00 AC: 0 AN: 22854

South Asian (SAS) AF: 0.00 AC: 0 AN: 3028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20818

Middle Eastern (MID) AF: 0.00156 AC: 2 AN: 1286

European-Non Finnish (NFE) AF: 0.000229 AC: 36 AN: 157464

Other (OTH) AF: 0.000858 AC: 14 AN: 16310

GnomAD4 genome AF: 0.000671 AC: 102 AN: 152122 Hom.: 0 Cov.: 32 AF XY: 0.000753 AC XY: 56 AN XY: 74360

African (AFR) AF: 0.00186 AC: 77 AN: 41500

American (AMR) AF: 0.000589 AC: 9 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 67996

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000899 Hom.: 0

Bravo AF: 0.000816

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
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.42
PhyloP100		0.011
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs28579899; hg19: chr3-170714485;