NM_030777.4:c.1547+18T>G

Variant names:

• chr20-46729506-T-G
• rs2425906
• NM_030777.4:c.1547+18T>G

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.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:8
• Conservation: PhyloP100: -2.87
• Publications: 8 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=-0.85).
• BP6: Variant 20-46729506-T-G is Benign according to our data. Variant chr20-46729506-T-G is described in ClinVar as Benign. ClinVar VariationId is 139178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030777.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A10	NM_030777.4	MANE Select	c.1547+18T>G		intron	N/A	NP_110404.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A10	ENST00000359271.4	TSL:1 MANE Select	c.1547+18T>G		intron	N/A	ENSP00000352216.2

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

GnomAD2 exomes AF: 0.418 AC: 104878 AN: 250922 AF XY: 0.417

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 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

African (AFR) AF: 0.210 AC: 7015 AN: 33434

American (AMR) AF: 0.423 AC: 18887 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 11360 AN: 26116

East Asian (EAS) AF: 0.601 AC: 23832 AN: 39662

South Asian (SAS) AF: 0.346 AC: 29846 AN: 86180

European-Finnish (FIN) AF: 0.443 AC: 23611 AN: 53302

Middle Eastern (MID) AF: 0.367 AC: 2112 AN: 5748

European-Non Finnish (NFE) AF: 0.422 AC: 468848 AN: 1109966

Other (OTH) AF: 0.416 AC: 25095 AN: 60300

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

African (AFR) AF: 0.219 AC: 9067 AN: 41338

American (AMR) AF: 0.446 AC: 6809 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1484 AN: 3472

East Asian (EAS) AF: 0.599 AC: 3085 AN: 5146

South Asian (SAS) AF: 0.341 AC: 1635 AN: 4794

European-Finnish (FIN) AF: 0.459 AC: 4800 AN: 10460

Middle Eastern (MID) AF: 0.379 AC: 110 AN: 290

European-Non Finnish (NFE) AF: 0.424 AC: 28787 AN: 67912

Other (OTH) AF: 0.408 AC: 857 AN: 2102

Alfa AF: 0.323 Hom.: 1494

Bravo AF: 0.370

Asia WGS AF: 0.426 AC: 1478 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Nov 20, 2012

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.

Aug 12, 2019

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Arterial tortuosity syndrome Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.027
DANN	Benign	0.58
PhyloP100		-2.9
Mutation Taster		=9/91	disease causing

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