3-170997427-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000340.2(SLC2A2):c.*476T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 159,486 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (46 hom., cov: 32)
  • Exomes 𝑓: 0.00097 (0 hom.)
• Consequence: SLC2A2 NM_000340.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0560

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-170997427-A-G is Benign according to our data. Variant chr3-170997427-A-G is described in ClinVar as [Benign]. Clinvar id is 344150.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1922/152236) while in subpopulation AFR AF= 0.0439 (1824/41562). AF 95% confidence interval is 0.0422. There are 46 homozygotes in gnomad4. There are 932 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A2	NM_000340.2	c.*476T>C		3_prime_UTR_variant	11/11	ENST00000314251.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A2	ENST00000314251.8	c.*476T>C		3_prime_UTR_variant	11/11	1	NM_000340.2	P1
SLC2A2	ENST00000497642.5	c.*1518T>C		3_prime_UTR_variant, NMD_transcript_variant	10/10	1
	ENST00000655926.1	n.291+2402A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1901 AN: 152118 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.0435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00439

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: 0.000132

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.000966 AC: 7 AN: 7250 Hom.: 0 Cov.: 0 AF XY: 0.000984 AC XY: 4 AN XY: 4064

Gnomad4 AFR exome AF: 0.0435

Gnomad4 AMR exome AF: 0.00250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000388

Gnomad4 OTH exome AF: 0.00357

GnomAD4 genome AF: 0.0126 AC: 1922 AN: 152236 Hom.: 46 Cov.: 32 AF XY: 0.0125 AC XY: 932 AN XY: 74436

Gnomad4 AFR AF: 0.0439

Gnomad4 AMR AF: 0.00438

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00549 Hom.: 4

Bravo AF: 0.0142

Asia WGS AF: 0.00434 AC: 15 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Fanconi-Bickel syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.1
Dann	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs75975646; hg19: chr3-170715216;