20-46709710-C-T

Variant names:

• chr20-46709710-C-T
• rs149481442
• NM_030777.4:c.-27C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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:3
• Conservation: PhyloP100: -0.0300
• Publications: 3 publications found

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]

SLC2A10 Gene-Disease associations (from GenCC):

• arterial tortuosity syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A10	NM_030777.4	c.-27C>T		5_prime_UTR_variant	Exon 1 of 5	ENST00000359271.4	NP_110404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A10	ENST00000359271.4	c.-27C>T		5_prime_UTR_variant	Exon 1 of 5	1	NM_030777.4	ENSP00000352216.2
SLC2A10	ENST00000486000.2	c.-27C>T		5_prime_UTR_variant	Exon 1 of 2	3		ENSP00000478679.1

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

GnomAD2 exomes AF: 0.0131 AC: 1732 AN: 132646 AF XY: 0.0129

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 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

African (AFR) AF: 0.00423 AC: 128 AN: 30282

American (AMR) AF: 0.0102 AC: 360 AN: 35316

Ashkenazi Jewish (ASJ) AF: 0.00965 AC: 240 AN: 24882

East Asian (EAS) AF: 0.0000286 AC: 1 AN: 34924

South Asian (SAS) AF: 0.00759 AC: 596 AN: 78504

European-Finnish (FIN) AF: 0.0262 AC: 1248 AN: 47604

Middle Eastern (MID) AF: 0.0199 AC: 86 AN: 4322

European-Non Finnish (NFE) AF: 0.0157 AC: 16872 AN: 1076338

Other (OTH) AF: 0.0134 AC: 771 AN: 57594

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

African (AFR) AF: 0.00279 AC: 116 AN: 41550

American (AMR) AF: 0.0122 AC: 187 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00950 AC: 33 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00745 AC: 36 AN: 4832

European-Finnish (FIN) AF: 0.0274 AC: 291 AN: 10622

Middle Eastern (MID) AF: 0.0479 AC: 14 AN: 292

European-Non Finnish (NFE) AF: 0.0169 AC: 1152 AN: 67966

Other (OTH) AF: 0.0142 AC: 30 AN: 2112

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Feb 01, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Arterial tortuosity syndrome Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		-0.030
PromoterAI		0.098	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=297/3	polymorphism

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: rs149481442; hg19: chr20-45338349;