chr20-46736010-T-C

Position:

• chr20-46736010-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.97).
• BP6: Variant 20-46736010-T-C is Benign according to our data. Variant chr20-46736010-T-C is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	Protein	UniProt
SLC2A10	NM_030777.4	c.*2176T>C		3_prime_UTR_variant	5/5	ENST00000359271.4	NP_110404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A10	ENST00000359271.4	c.*2176T>C		3_prime_UTR_variant	5/5	1	NM_030777.4	ENSP00000352216	P1

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

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

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.603

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.426

Alfa AF: 0.407 Hom.: 5131

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Arterial tortuosity 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.16
DANN	Benign	0.35

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: rs1059217; hg19: chr20-45364649;