NM_006516.4:c.*587A>T

Variant names:

• chr1-42926454-T-A
• rs748209315
• NM_006516.4:c.*587A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006516.4(SLC2A1):​c.*587A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 242,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: SLC2A1 NM_006516.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 0.391
• Publications: 0 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: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• GLUT1 deficiency syndrome

  Inheritance: SD, AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, ClinGen
• childhood onset GLUT1 deficiency syndrome 2

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006516.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A1	NM_006516.4	MANE Select	c.*587A>T		3_prime_UTR	Exon 10 of 10	NP_006507.2	P11166

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A1	ENST00000426263.10	TSL:1 MANE Select	c.*587A>T		3_prime_UTR	Exon 10 of 10	ENSP00000416293.2	P11166
	SLC2A1	ENST00000889577.1		c.*587A>T		3_prime_UTR	Exon 10 of 10	ENSP00000559636.1
	SLC2A1	ENST00000958848.1		c.*587A>T		3_prime_UTR	Exon 10 of 10	ENSP00000628907.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151972 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000222 AC: 2 AN: 90134 Hom.: 0 Cov.: 2 AF XY: 0.0000207 AC XY: 1 AN XY: 48344

African (AFR) AF: 0.00 AC: 0 AN: 3340

American (AMR) AF: 0.00 AC: 0 AN: 6478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1926

East Asian (EAS) AF: 0.00 AC: 0 AN: 5440

South Asian (SAS) AF: 0.00 AC: 0 AN: 14948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 318

European-Non Finnish (NFE) AF: 0.0000404 AC: 2 AN: 49458

Other (OTH) AF: 0.00 AC: 0 AN: 4326

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151972 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74200

African (AFR) AF: 0.00 AC: 0 AN: 41360

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Dystonia 9 (1)
-	1	-	Encephalopathy due to GLUT1 deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		0.39
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	polymorphism

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: rs748209315; hg19: chr1-43392125;