chr20-46725566-T-G

Variant names:

• chr20-46725566-T-G
• rs777214287
• NM_030777.4:c.530T>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_030777.4(SLC2A10):​c.530T>G​(p.Leu177Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L177P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC2A10 NM_030777.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08
• Publications: 0 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.972

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.530T>G	p.Leu177Arg	missense	Exon 2 of 5	NP_110404.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A10	ENST00000359271.4	TSL:1 MANE Select	c.530T>G	p.Leu177Arg	missense	Exon 2 of 5	ENSP00000352216.2
	SLC2A10	ENST00000611837.1	TSL:2	n.*96T>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.80	D
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	0.72	D
MutationAssessor	Pathogenic	3.5	H
PhyloP100		4.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.018	D
Polyphen		0.97	D
Vest4		0.67
MutPred		0.88		Gain of methylation at L177 (P = 0.0084)
MVP		0.89
MPC		0.44
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.97
gMVP		0.84
Mutation Taster		=72/28	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: rs777214287; hg19: chr20-45354205;