chr1-42929018-G-T

Variant names:

• chr1-42929018-G-T
• rs80359826
• NM_006516.4:c.988C>A
• SLC2A1 p.Arg330Arg

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-3 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -3 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_ModerateBP6_ModerateBP7

The NM_006516.4(SLC2A1):c.988C>A (p.Arg330Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC2A1 NM_006516.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.55
• Publications: 14 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), Orphanet, G2P
• 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: Genomics England PanelApp, Orphanet
• dystonia 9

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
• 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

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -3 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD+AR) (threshold 0.0001) — PM2 moderate.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Moderate).
	BP6Reputable source reports benign		ClinVar 1-star benign — moderate (BP6); ClinVar germline classification: Benign/Likely Benign, 1 star(s).
	BP7Synonymous variant, no splicing impact		Synonymous variant at non-conserved position with no predicted splicing impact (BP7); Synonymous at non-conserved position, no splicing concern — benign (BP7).

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	SLC2A1 NM_006516.4	MANE Select	c.988C>A p.Arg330Arg	synonymous	Exon 8 of 10	Prot: NP_006507.2 UniProt:

SLC2A1 NM_006516.4

MANE Select

HGVSc / HGVSpc.988C>Ap.Arg330Arg

Exon rankExon 8 of 10

synonymous

Prot: NP_006507.2UniProt: P11166

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	SLC2A1 ENST00000426263.10	TSL:1MANE Select	c.988C>A p.Arg330Arg	synonymous	Exon 8 of 10	Prot: ENSP00000416293.2 UniProt:
	SLC2A1 ENST00000889577.1		c.985C>A p.Arg329Arg	synonymous	Exon 8 of 10	Prot: ENSP00000559636.1 UniProt:
	SLC2A1 ENST00000958848.1		c.988C>A p.Arg330Arg	synonymous	Exon 8 of 10	Prot: ENSP00000628907.1 UniProt:

SLC2A1 ENST00000426263.10

TSL:1MANE Select

HGVSc / HGVSpc.988C>Ap.Arg330Arg

Exon rankExon 8 of 10

synonymous

Prot: ENSP00000416293.2UniProt: P11166

SLC2A1 ENST00000889577.1

HGVSc / HGVSpc.985C>Ap.Arg329Arg

Exon rankExon 8 of 10

synonymous

Prot: ENSP00000559636.1UniProt: A0ACI8RFT3

SLC2A1 ENST00000958848.1

HGVSc / HGVSpc.988C>Ap.Arg330Arg

Exon rankExon 8 of 10

synonymous

Prot: ENSP00000628907.1UniProt: A0ACI8V0G7

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:33
GnomAD2 exomes	AF: 0.00000400	AC:1	Hom:	AN:250150	Cov:
GnomAD4 exome Warning	AF: 0.00	AC:0	Hom:0	AN:1460872	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:33

Showing 4 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
SCHEMA(Schizophrenia)	0.0000772	1	12950	0.00	0	23216

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	GLUT1 deficiency syndrome 1, autosomal recessive (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	18
BayesDel_noAF	Benign	-0.42
CADD	Benign	12
DANN	Benign	0.93
GPN-Star LLR	N/A	-3.6
GPN-Star score	N/A	3.6
Mutation Taster	N/A	100/0	polymorphism
PhyloP100	Uncertain	4.5
RBP_binding_hub_radar	N/A	0.92
RBP_regulation_power_radar	N/A	2.6

Showing 10 of 10 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.010
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs80359826;

hg19: chr1-43394689;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar