rs998422

Variant names:

• chr20-46730769-A-G
• rs998422
• NM_030777.4:c.1547+1281A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030777.4(SLC2A10):​c.1547+1281A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,962 control chromosomes in the GnomAD database, including 10,807 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (10807 hom., cov: 31)
• Consequence: SLC2A10 NM_030777.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 11 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A10	NM_030777.4	c.1547+1281A>G		intron_variant	Intron 4 of 4	ENST00000359271.4	NP_110404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A10	ENST00000359271.4	c.1547+1281A>G		intron_variant	Intron 4 of 4	1	NM_030777.4	ENSP00000352216.2

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53676 AN: 151844 Hom.: 10797 Cov.: 31

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.391

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.353 AC: 53708 AN: 151962 Hom.: 10807 Cov.: 31 AF XY: 0.358 AC XY: 26609 AN XY: 74260

African (AFR) AF: 0.154 AC: 6394 AN: 41460

American (AMR) AF: 0.438 AC: 6683 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1483 AN: 3464

East Asian (EAS) AF: 0.585 AC: 3017 AN: 5160

South Asian (SAS) AF: 0.340 AC: 1637 AN: 4812

European-Finnish (FIN) AF: 0.429 AC: 4526 AN: 10548

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28706 AN: 67934

Other (OTH) AF: 0.392 AC: 828 AN: 2112

Alfa AF: 0.401 Hom.: 9989

Bravo AF: 0.348

Asia WGS AF: 0.414 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.0
DANN	Benign	0.75
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs998422; hg19: chr20-45359408;