chr1-42929613-G-A

Variant names:

• chr1-42929613-G-A
• rs587784397
• NM_006516.4:c.847C>T

Variant summary

Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1 PM2 PP5_Very_Strong

The NM_006516.4(SLC2A1):​c.847C>T​(p.Gln283*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC2A1 NM_006516.4 stop_gained
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:5
• Conservation: PhyloP100: 10.0
• Publications: 3 publications found

Genes affected

SLC2A1 (HGNC:11005): (solute carrier family 2 member 1) This gene encodes a major glucose transporter in the mammalian blood-brain barrier. The encoded protein is found primarily in the cell membrane and on the cell surface, where it can also function as a receptor for human T-cell leukemia virus (HTLV) I and II. Mutations in this gene have been found in a family with paroxysmal exertion-induced dyskinesia. [provided by RefSeq, Apr 2013]

SLC2A1 Gene-Disease associations (from GenCC):

• encephalopathy due to GLUT1 deficiency

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• GLUT1 deficiency syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• childhood onset GLUT1 deficiency syndrome 2

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
• dystonia 9

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• epilepsy, idiopathic generalized, susceptibility to, 12

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• childhood absence epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary cryohydrocytosis with reduced stomatin

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• myoclonic-astatic epilepsy

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 18 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-42929613-G-A is Pathogenic according to our data. Variant chr1-42929613-G-A is described in CliVar as Pathogenic. Clinvar id is 159930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-42929613-G-A is described in CliVar as Pathogenic. Clinvar id is 159930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-42929613-G-A is described in CliVar as Pathogenic. Clinvar id is 159930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-42929613-G-A is described in CliVar as Pathogenic. Clinvar id is 159930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-42929613-G-A is described in CliVar as Pathogenic. Clinvar id is 159930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-42929613-G-A is described in CliVar as Pathogenic. Clinvar id is 159930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-42929613-G-A is described in CliVar as Pathogenic. Clinvar id is 159930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-42929613-G-A is described in CliVar as Pathogenic. Clinvar id is 159930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-42929613-G-A is described in CliVar as Pathogenic. Clinvar id is 159930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-42929613-G-A is described in CliVar as Pathogenic. Clinvar id is 159930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-42929613-G-A is described in CliVar as Pathogenic. Clinvar id is 159930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A1	NM_006516.4	c.847C>T	p.Gln283*	stop_gained	Exon 6 of 10	ENST00000426263.10	NP_006507.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A1	ENST00000426263.10	c.847C>T	p.Gln283*	stop_gained	Exon 6 of 10	1	NM_006516.4	ENSP00000416293.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Encephalopathy due to GLUT1 deficiency Pathogenic:3

Sep 17, 2014

Courtagen Diagnostics Laboratory, Courtagen Life Sciences

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 11, 2023

Genome-Nilou Lab

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Pathogenic:1

Nov 11, 2022

Revvity Omics, Revvity

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Seizure Pathogenic:1

Apr 18, 2025

Génétique des Maladies du Développement, Hospices Civils de Lyon

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.56
CADD	Pathogenic	42
DANN	Uncertain	1.0
Eigen	Pathogenic	1.2
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.98	D
PhyloP100		10
Vest4		0.96
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=2/198	disease causing (ClinVar)

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: rs587784397; hg19: chr1-43395284;