chr20-46736010-T-C

Variant names:

• chr20-46736010-T-C
• rs1059217
• NM_030777.4:c.*2176T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_030777.4(SLC2A10):​c.*2176T>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 0.406 in 152,024 control chromosomes in the GnomAD database, including 12,967 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (12967 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SLC2A10 NM_030777.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.46
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 20-46736010-T-C is Benign according to our data. Variant chr20-46736010-T-C is described in ClinVar as Benign. ClinVar VariationId is 338631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A10	NM_030777.4	c.*2176T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000359271.4	NP_110404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A10	ENST00000359271.4	c.*2176T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_030777.4	ENSP00000352216.2

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61697 AN: 151908 Hom.: 12958 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.424

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.406 AC: 61736 AN: 152024 Hom.: 12967 Cov.: 32 AF XY: 0.411 AC XY: 30525 AN XY: 74306

African (AFR) AF: 0.317 AC: 13150 AN: 41494

American (AMR) AF: 0.457 AC: 6978 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1541 AN: 3464

East Asian (EAS) AF: 0.603 AC: 3118 AN: 5168

South Asian (SAS) AF: 0.400 AC: 1927 AN: 4816

European-Finnish (FIN) AF: 0.456 AC: 4802 AN: 10536

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.425 AC: 28886 AN: 67952

Other (OTH) AF: 0.426 AC: 900 AN: 2112

Alfa AF: 0.411 Hom.: 6195

Bravo AF: 0.403

Asia WGS AF: 0.463 AC: 1609 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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 13, 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	-0.97
CADD	Benign	0.16
DANN	Benign	0.35
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs1059217; hg19: chr20-45364649;