20-46725546-G-A

Variant names:

• chr20-46725546-G-A
• rs80358229
• NM_030777.4:c.510G>A
• SLC2A10 p.Trp170*

GermlineCancer (beta)

Variant summary

Our verdict is Pathogenic.

>+14 Pathogenic

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 18 classification points (ACMG Germline Pathogenicity v2019). PVS1PM2PP5_Very_Strong

The NM_030777.4(SLC2A10):c.510G>A (p.Trp170*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant is predicted to lead to nonsense-mediated mRNA decay (NMD). 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 damaging/oncogenic. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic/Likely Pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC2A10 NM_030777.4 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:5 O:1
• Conservation: PhyloP100: 3.31
• Publications: 4 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: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics, PanelApp Australia

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Pathogenic. The variant received 18 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PVS1Null variant in LOF gene		Frameshift/stop-gained, NMD predicted, LoF disease mechanism — very strong (PVS1); Stop-gained (exon 2 of 5) at amino acid 170 of 541, predicted to trigger nonsense-mediated mRNA decay. Loss of function is a known disease mechanism for this gene.
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: AR) (threshold 0.001) — PM2 moderate.
	PP5Reputable source reports pathogenic		ClinVar 1-star pathogenic but pathogenic submissions clearly dominant — very strong (PP5); ClinVar germline classification: Pathogenic/Likely Pathogenic, 1 star(s).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_030777.4. 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
	SLC2A10 NM_030777.4	MANE Select	c.510G>A p.Trp170*	stop_gained	Exon 2 of 5	Prot: NP_110404.1 UniProt:

SLC2A10 NM_030777.4

MANE Select

HGVSc / HGVSpc.510G>Ap.Trp170*

Exon rankExon 2 of 5

stop_gained

Prot: NP_110404.1UniProt: O95528

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	SLC2A10 ENST00000359271.4	TSL:1MANE Select	c.510G>A p.Trp170*	stop_gained	Exon 2 of 5	Prot: ENSP00000352216.2 UniProt:
	SLC2A10 ENST00000862794.1		c.804G>A p.Trp268*	stop_gained	Exon 2 of 5	Prot: ENSP00000532853.1 UniProt:
	SLC2A10 ENST00000862792.1		c.510G>A p.Trp170*	stop_gained	Exon 2 of 6	Prot: ENSP00000532851.1 UniProt:

SLC2A10 ENST00000359271.4

TSL:1MANE Select

HGVSc / HGVSpc.510G>Ap.Trp170*

Exon rankExon 2 of 5

stop_gained

Prot: ENSP00000352216.2UniProt: O95528

SLC2A10 ENST00000862794.1

HGVSc / HGVSpc.804G>Ap.Trp268*

Exon rankExon 2 of 5

stop_gained

Prot: ENSP00000532853.1UniProt: A0ACI8PFL4

SLC2A10 ENST00000862792.1

HGVSc / HGVSpc.510G>Ap.Trp170*

Exon rankExon 2 of 6

stop_gained

Prot: ENSP00000532851.1UniProt: A0ACI8PM99

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
GnomAD4 exome	AF:	AC:	Hom:	AN:	Cov:33
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:33
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.0000655	AC:1	Hom:0	AN:15260	Cov:

Showing 4 sources

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
3	-	-	Arterial tortuosity syndrome (4)
2	-	-	not provided (2)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Pathogenic	39
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Uncertain	0.95	D
GPN-Star LLR	N/A	-9.9
GPN-Star score	N/A	9.9
Mutation Taster	N/A	7/193	disease causing (ClinVar)
PhyloP100	Benign	3.3

Showing 12 of 12 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: rs80358229;

hg19: chr20-45354185;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar