20-46735127-T-C

Variant names:

• chr20-46735127-T-C
• rs707507
• NM_030777.4:c.*1293T>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.*1293T>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 0.388 in 152,528 control chromosomes in the GnomAD database, including 12,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12065 hom., cov: 32)
  • Exomes 𝑓: 0.40 (33 hom.)
• Consequence: SLC2A10 NM_030777.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.17
• Publications: 10 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=-1.02).
• BP6: Variant 20-46735127-T-C is Benign according to our data. Variant chr20-46735127-T-C is described in ClinVar as [Benign]. Clinvar id is 338623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A10	NM_030777.4	c.*1293T>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.*1293T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_030777.4	ENSP00000352216.2

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58879 AN: 151956 Hom.: 12041 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.414

GnomAD4 exome AF: 0.396 AC: 180 AN: 454 Hom.: 33 Cov.: 0 AF XY: 0.391 AC XY: 108 AN XY: 276

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.393 AC: 162 AN: 412

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.467 AC: 14 AN: 30

Other (OTH) AF: 0.250 AC: 2 AN: 8

GnomAD4 genome AF: 0.388 AC: 58938 AN: 152074 Hom.: 12065 Cov.: 32 AF XY: 0.392 AC XY: 29154 AN XY: 74332

African (AFR) AF: 0.262 AC: 10860 AN: 41488

American (AMR) AF: 0.450 AC: 6875 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1547 AN: 3470

East Asian (EAS) AF: 0.586 AC: 3023 AN: 5160

South Asian (SAS) AF: 0.400 AC: 1927 AN: 4818

European-Finnish (FIN) AF: 0.430 AC: 4547 AN: 10580

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.424 AC: 28851 AN: 67978

Other (OTH) AF: 0.415 AC: 870 AN: 2098

Alfa AF: 0.414 Hom.: 16711

Bravo AF: 0.384

Asia WGS AF: 0.452 AC: 1569 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	-1.0
CADD	Benign	0.51
DANN	Benign	0.20
PhyloP100		-1.2
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: rs707507; hg19: chr20-45363766;