20-46709710-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_030777.4(SLC2A10):c.-27C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,541,988 control chromosomes in the GnomAD database, including 187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (19 hom., cov: 33)
  • Exomes 𝑓: 0.015 (168 hom.)
• Consequence: SLC2A10 NM_030777.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0300

Genes affected

SLC2A10 (HGNC:13444): (solute carrier family 2 member 10) This gene encodes a member of the class III facilitative glucose transporter family. The encoded protein plays a role in regulation of glucose homeostasis. Mutations in this gene have been associated with arterial tortuosity syndrome.[provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 20-46709710-C-T is Benign according to our data. Variant chr20-46709710-C-T is described in ClinVar as [Benign]. Clinvar id is 139184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-46709710-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0127 (1934/152222) while in subpopulation NFE AF= 0.0169 (1152/67966). AF 95% confidence interval is 0.0161. There are 19 homozygotes in gnomad4. There are 1004 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A10	NM_030777.4	c.-27C>T		5_prime_UTR_variant	1/5	ENST00000359271.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A10	ENST00000359271.4	c.-27C>T		5_prime_UTR_variant	1/5	1	NM_030777.4	P1
SLC2A10	ENST00000486000.2	c.-27C>T		5_prime_UTR_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1935 AN: 152110 Hom.: 19 Cov.: 33

Gnomad AFR AF: 0.00275

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00765

Gnomad FIN AF: 0.0274

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0144

GnomAD3 exomes AF: 0.0131 AC: 1732 AN: 132646 Hom.: 12 AF XY: 0.0129 AC XY: 929 AN XY: 72196

Gnomad AFR exome AF: 0.00318

Gnomad AMR exome AF: 0.0101

Gnomad ASJ exome AF: 0.00855

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00731

Gnomad FIN exome AF: 0.0281

Gnomad NFE exome AF: 0.0166

Gnomad OTH exome AF: 0.0172

GnomAD4 exome AF: 0.0146 AC: 20302 AN: 1389766 Hom.: 168 Cov.: 30 AF XY: 0.0146 AC XY: 10016 AN XY: 685488

Gnomad4 AFR exome AF: 0.00423

Gnomad4 AMR exome AF: 0.0102

Gnomad4 ASJ exome AF: 0.00965

Gnomad4 EAS exome AF: 0.0000286

Gnomad4 SAS exome AF: 0.00759

Gnomad4 FIN exome AF: 0.0262

Gnomad4 NFE exome AF: 0.0157

Gnomad4 OTH exome AF: 0.0134

GnomAD4 genome AF: 0.0127 AC: 1934 AN: 152222 Hom.: 19 Cov.: 33 AF XY: 0.0135 AC XY: 1004 AN XY: 74424

Gnomad4 AFR AF: 0.00279

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00745

Gnomad4 FIN AF: 0.0274

Gnomad4 NFE AF: 0.0169

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0140 Hom.: 6

Bravo AF: 0.0113

Asia WGS AF: 0.00347 AC: 12 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 01, 2013

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Arterial tortuosity 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	-0.74
Cadd	Benign	14
Dann	Benign	0.95
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

Publications

LitVar

Other links and lift over

dbSNP: rs149481442; hg19: chr20-45338349;