chr3-170996646-G-A

Position:

• chr3-170996646-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000340.2(SLC2A2):​c.*1257C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 397,696 control chromosomes in the GnomAD database, including 6,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3703 hom., cov: 32)
  • Exomes 𝑓: 0.13 (2600 hom.)
• Consequence: SLC2A2 NM_000340.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.650

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]

ENSG00000286856 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-170996646-G-A is Benign according to our data. Variant chr3-170996646-G-A is described in ClinVar as [Benign]. Clinvar id is 344137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A2	NM_000340.2	c.*1257C>T		3_prime_UTR_variant	11/11	ENST00000314251.8	NP_000331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A2	ENST00000314251	c.*1257C>T		3_prime_UTR_variant	11/11	1	NM_000340.2	ENSP00000323568.3
ENSG00000286856	ENST00000655926.1	n.291+1621G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29494 AN: 151892 Hom.: 3695 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.00944

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.132 AC: 32524 AN: 245686 Hom.: 2600 Cov.: 0 AF XY: 0.131 AC XY: 16370 AN XY: 124512

Gnomad4 AFR exome AF: 0.363

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.0205

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.151

GnomAD4 genome AF: 0.194 AC: 29533 AN: 152010 Hom.: 3703 Cov.: 32 AF XY: 0.193 AC XY: 14353 AN XY: 74308

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.00947

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.182

Alfa AF: 0.190 Hom.: 512

Bravo AF: 0.202

Asia WGS AF: 0.104 AC: 366 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Fanconi-Bickel syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.58

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: rs55679742; hg19: chr3-170714435;