rs117587497

Variant names:

• chr20-46729453-G-A
• rs117587497
• NM_030777.4:c.1512G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_030777.4(SLC2A10):​c.1512G>A​(p.Ser504Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,613,958 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0013 (5 hom.)
• Consequence: SLC2A10 NM_030777.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:11
• Conservation: PhyloP100: -5.05
• Publications: 2 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: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 20-46729453-G-A is Benign according to our data. Variant chr20-46729453-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 139176.
• BP7: Synonymous conserved (PhyloP=-5.05 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00129 (197/152144) while in subpopulation NFE AF = 0.00193 (131/68000). AF 95% confidence interval is 0.00166. There are 0 homozygotes in GnomAd4. There are 87 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR,AD gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A10	NM_030777.4	MANE Select	c.1512G>A	p.Ser504Ser	synonymous	Exon 4 of 5	NP_110404.1	O95528

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A10	ENST00000359271.4	TSL:1 MANE Select	c.1512G>A	p.Ser504Ser	synonymous	Exon 4 of 5	ENSP00000352216.2	O95528
	SLC2A10	ENST00000862794.1		c.1806G>A	p.Ser602Ser	synonymous	Exon 4 of 5	ENSP00000532853.1
	SLC2A10	ENST00000862792.1		c.1644G>A	p.Ser548Ser	synonymous	Exon 5 of 6	ENSP00000532851.1

Frequencies

GnomAD3 genomes AF: 0.00130 AC: 197 AN: 152026 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000832

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00193

Gnomad OTH AF: 0.00336

GnomAD2 exomes AF: 0.00143 AC: 360 AN: 251490 AF XY: 0.00155

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00228

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000508

Gnomad NFE exome AF: 0.00199

Gnomad OTH exome AF: 0.00358

GnomAD4 exome AF: 0.00132 AC: 1930 AN: 1461814 Hom.: 5 Cov.: 32 AF XY: 0.00140 AC XY: 1020 AN XY: 727222

African (AFR) AF: 0.000508 AC: 17 AN: 33480

American (AMR) AF: 0.00165 AC: 74 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00272 AC: 71 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000916 AC: 79 AN: 86258

European-Finnish (FIN) AF: 0.000468 AC: 25 AN: 53410

Middle Eastern (MID) AF: 0.00954 AC: 55 AN: 5764

European-Non Finnish (NFE) AF: 0.00131 AC: 1459 AN: 1111968

Other (OTH) AF: 0.00248 AC: 150 AN: 60388

GnomAD4 genome AF: 0.00129 AC: 197 AN: 152144 Hom.: 0 Cov.: 31 AF XY: 0.00117 AC XY: 87 AN XY: 74388

African (AFR) AF: 0.000241 AC: 10 AN: 41510

American (AMR) AF: 0.00164 AC: 25 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000833 AC: 4 AN: 4802

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10598

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00193 AC: 131 AN: 68000

Other (OTH) AF: 0.00332 AC: 7 AN: 2108

Alfa AF: 0.00137 Hom.: 0

Bravo AF: 0.00125

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	4	Arterial tortuosity syndrome (5)
-	-	3	not specified (3)
-	-	2	Familial thoracic aortic aneurysm and aortic dissection (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.0080
DANN	Benign	0.66
PhyloP100		-5.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs117587497; hg19: chr20-45358092; COSMIC: COSV63714906; COSMIC: COSV63714906;