20-46725402-C-T

Variant names:

• chr20-46725402-C-T
• rs34990188
• NM_030777.4:c.366C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_030777.4(SLC2A10):​c.366C>T​(p.Tyr122Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00507 in 1,614,168 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0052 (30 hom.)
• Consequence: SLC2A10 NM_030777.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -2.40
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 20-46725402-C-T is Benign according to our data. Variant chr20-46725402-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 139171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.4 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00418 (636/152318) while in subpopulation AMR AF = 0.00771 (118/15304). AF 95% confidence interval is 0.00658. There are 3 homozygotes in GnomAd4. There are 293 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 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.366C>T	p.Tyr122Tyr	synonymous	Exon 2 of 5	NP_110404.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A10	ENST00000359271.4	TSL:1 MANE Select	c.366C>T	p.Tyr122Tyr	synonymous	Exon 2 of 5	ENSP00000352216.2
	SLC2A10	ENST00000862794.1		c.660C>T	p.Tyr220Tyr	synonymous	Exon 2 of 5	ENSP00000532853.1
	SLC2A10	ENST00000862792.1		c.366C>T	p.Tyr122Tyr	synonymous	Exon 2 of 6	ENSP00000532851.1

Frequencies

GnomAD3 genomes AF: 0.00419 AC: 637 AN: 152200 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00621

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00545

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00472 AC: 1185 AN: 251232 AF XY: 0.00485

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00515

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00329

Gnomad NFE exome AF: 0.00563

Gnomad OTH exome AF: 0.00619

GnomAD4 exome AF: 0.00516 AC: 7541 AN: 1461850 Hom.: 30 Cov.: 33 AF XY: 0.00523 AC XY: 3805 AN XY: 727232

African (AFR) AF: 0.000717 AC: 24 AN: 33480

American (AMR) AF: 0.00624 AC: 279 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00356 AC: 93 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00671 AC: 579 AN: 86258

European-Finnish (FIN) AF: 0.00268 AC: 143 AN: 53380

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.00549 AC: 6108 AN: 1112008

Other (OTH) AF: 0.00500 AC: 302 AN: 60396

GnomAD4 genome AF: 0.00418 AC: 636 AN: 152318 Hom.: 3 Cov.: 33 AF XY: 0.00393 AC XY: 293 AN XY: 74478

African (AFR) AF: 0.00125 AC: 52 AN: 41572

American (AMR) AF: 0.00771 AC: 118 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4828

European-Finnish (FIN) AF: 0.00339 AC: 36 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00545 AC: 371 AN: 68024

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00462 Hom.: 1

Bravo AF: 0.00468

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00687

EpiControl AF: 0.00699

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	4	Arterial tortuosity syndrome (4)
-	-	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	-0.69
CADD	Benign	1.5
DANN	Benign	0.51
PhyloP100		-2.4
Mutation Taster		=100/0	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: rs34990188; hg19: chr20-45354041; COSMIC: COSV63714081;