3-170998041-G-A

Variant names:

• chr3-170998041-G-A
• rs5398
• NM_000340.2:c.1437C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_000340.2(SLC2A2):​c.1437C>T​(p.Phe479Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,613,122 control chromosomes in the GnomAD database, including 78,050 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.38 (12175 hom., cov: 32)
  • Exomes 𝑓: 0.30 (65875 hom.)
• Consequence: SLC2A2 NM_000340.2 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:8
• Conservation: PhyloP100: -0.739
• Publications: 44 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 3-170998041-G-A is Benign according to our data. Variant chr3-170998041-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 130348.
• BP7: Synonymous conserved (PhyloP=-0.739 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

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.1437C>T	p.Phe479Phe	synonymous	Exon 11 of 11	NP_000331.1	P11168-1
	SLC2A2	NM_001278658.2		c.1080C>T	p.Phe360Phe	synonymous	Exon 10 of 10	NP_001265587.1	P11168-2
	SLC2A2	NM_001278659.2		c.918C>T	p.Phe306Phe	synonymous	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.1437C>T	p.Phe479Phe	synonymous	Exon 11 of 11	ENSP00000323568.3	P11168-1
	SLC2A2	ENST00000497642.5	TSL:1	n.*904C>T		non_coding_transcript_exon	Exon 10 of 10	ENSP00000418456.1	A0A0C4DH64
	SLC2A2	ENST00000497642.5	TSL:1	n.*904C>T		3_prime_UTR	Exon 10 of 10	ENSP00000418456.1	A0A0C4DH64

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56935 AN: 151836 Hom.: 12148 Cov.: 32

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.366

GnomAD2 exomes AF: 0.307 AC: 76887 AN: 250066 AF XY: 0.304

Gnomad AFR exome AF: 0.602

Gnomad AMR exome AF: 0.285

Gnomad ASJ exome AF: 0.316

Gnomad EAS exome AF: 0.235

Gnomad FIN exome AF: 0.262

Gnomad NFE exome AF: 0.299

Gnomad OTH exome AF: 0.307

GnomAD4 exome AF: 0.295 AC: 431072 AN: 1461168 Hom.: 65875 Cov.: 37 AF XY: 0.293 AC XY: 213184 AN XY: 726908

African (AFR) AF: 0.605 AC: 20230 AN: 33452

American (AMR) AF: 0.291 AC: 12965 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 8271 AN: 26118

East Asian (EAS) AF: 0.223 AC: 8845 AN: 39692

South Asian (SAS) AF: 0.279 AC: 24029 AN: 86242

European-Finnish (FIN) AF: 0.263 AC: 14056 AN: 53388

Middle Eastern (MID) AF: 0.329 AC: 1897 AN: 5766

European-Non Finnish (NFE) AF: 0.289 AC: 321604 AN: 1111566

Other (OTH) AF: 0.318 AC: 19175 AN: 60344

GnomAD4 genome AF: 0.375 AC: 57005 AN: 151954 Hom.: 12175 Cov.: 32 AF XY: 0.371 AC XY: 27569 AN XY: 74260

African (AFR) AF: 0.595 AC: 24654 AN: 41458

American (AMR) AF: 0.340 AC: 5180 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3466

East Asian (EAS) AF: 0.231 AC: 1188 AN: 5150

South Asian (SAS) AF: 0.273 AC: 1315 AN: 4814

European-Finnish (FIN) AF: 0.244 AC: 2581 AN: 10564

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.292 AC: 19864 AN: 67946

Other (OTH) AF: 0.364 AC: 769 AN: 2110

Alfa AF: 0.323 Hom.: 31118

Bravo AF: 0.392

Asia WGS AF: 0.290 AC: 1012 AN: 3478

EpiCase AF: 0.301

EpiControl AF: 0.298

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Fanconi-Bickel syndrome (3)
-	-	1	not provided (1)
-	1	-	Type 2 diabetes mellitus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs5398; hg19: chr3-170715830; COSMIC: COSV58587971; COSMIC: COSV58587971;