20-46729506-T-G

Position:

• chr20-46729506-T-G

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.1547+18T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 1,611,072 control chromosomes in the GnomAD database, including 141,855 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11570 hom., cov: 31)
  • Exomes 𝑓: 0.42 (130285 hom.)
• Consequence: SLC2A10 NM_030777.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.87

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=-0.85).
• BP6: Variant 20-46729506-T-G is Benign according to our data. Variant chr20-46729506-T-G is described in ClinVar as [Benign]. Clinvar id is 139178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-46729506-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A10	NM_030777.4	c.1547+18T>G		intron_variant		ENST00000359271.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A10	ENST00000359271.4	c.1547+18T>G		intron_variant		1	NM_030777.4	P1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 56918 AN: 151560 Hom.: 11559 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.359

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.406

GnomAD3 exomes AF: 0.418 AC: 104878 AN: 250922 Hom.: 22616 AF XY: 0.417 AC XY: 56542 AN XY: 135740

Gnomad AFR exome AF: 0.216

Gnomad AMR exome AF: 0.422

Gnomad ASJ exome AF: 0.440

Gnomad EAS exome AF: 0.607

Gnomad SAS exome AF: 0.347

Gnomad FIN exome AF: 0.449

Gnomad NFE exome AF: 0.426

Gnomad OTH exome AF: 0.420

GnomAD4 exome AF: 0.418 AC: 610606 AN: 1459404 Hom.: 130285 Cov.: 38 AF XY: 0.416 AC XY: 302134 AN XY: 726134

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.423

Gnomad4 ASJ exome AF: 0.435

Gnomad4 EAS exome AF: 0.601

Gnomad4 SAS exome AF: 0.346

Gnomad4 FIN exome AF: 0.443

Gnomad4 NFE exome AF: 0.422

Gnomad4 OTH exome AF: 0.416

GnomAD4 genome AF: 0.376 AC: 56954 AN: 151668 Hom.: 11570 Cov.: 31 AF XY: 0.380 AC XY: 28180 AN XY: 74064

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.408

Alfa AF: 0.327 Hom.: 1477

Bravo AF: 0.370

Asia WGS AF: 0.426 AC: 1478 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 12, 2019	Variant summary: SLC2A10 c.1547+18T>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.42 in 250922 control chromosomes, predominantly at a frequency of 0.61 within the East Asian subpopulation in the gnomAD database, including 3377 homozygotes. Therefore, suggesting the variant is the major allele found in population(s) of East Asian origin. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 20, 2012	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. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Arterial tortuosity syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.027
DANN	Benign	0.58

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: rs2425906; hg19: chr20-45358145; COSMIC: COSV63714393; COSMIC: COSV63714393;