rs76315093

Variant names:

• chr20-46726334-G-A
• rs76315093
• NM_030777.4:c.1288+10G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_030777.4(SLC2A10):​c.1288+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 1,605,492 control chromosomes in the GnomAD database, including 196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0089 (6 hom., cov: 33)
  • Exomes 𝑓: 0.014 (190 hom.)
• Consequence: SLC2A10 NM_030777.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 1.14
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-46726334-G-A is Benign according to our data. Variant chr20-46726334-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 139175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00892 (1359/152286) while in subpopulation SAS AF = 0.0154 (74/4816). AF 95% confidence interval is 0.0133. There are 6 homozygotes in GnomAd4. There are 628 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 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.1288+10G>A		intron	N/A	NP_110404.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A10	ENST00000359271.4	TSL:1 MANE Select	c.1288+10G>A		intron	N/A	ENSP00000352216.2
	SLC2A10	ENST00000862794.1		c.1582+10G>A		intron	N/A	ENSP00000532853.1
	SLC2A10	ENST00000862792.1		c.1288+10G>A		intron	N/A	ENSP00000532851.1

Frequencies

GnomAD3 genomes AF: 0.00893 AC: 1359 AN: 152168 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00253

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.00798

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0154

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0141

Gnomad OTH AF: 0.0125

GnomAD2 exomes AF: 0.0103 AC: 2462 AN: 238094 AF XY: 0.0110

Gnomad AFR exome AF: 0.00233

Gnomad AMR exome AF: 0.00557

Gnomad ASJ exome AF: 0.00896

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00315

Gnomad NFE exome AF: 0.0143

Gnomad OTH exome AF: 0.0113

GnomAD4 exome AF: 0.0142 AC: 20567 AN: 1453206 Hom.: 190 Cov.: 33 AF XY: 0.0143 AC XY: 10350 AN XY: 723216

African (AFR) AF: 0.00248 AC: 83 AN: 33476

American (AMR) AF: 0.00604 AC: 270 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00857 AC: 224 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.0168 AC: 1445 AN: 86228

European-Finnish (FIN) AF: 0.00418 AC: 188 AN: 44946

Middle Eastern (MID) AF: 0.00937 AC: 54 AN: 5766

European-Non Finnish (NFE) AF: 0.0158 AC: 17573 AN: 1111920

Other (OTH) AF: 0.0121 AC: 728 AN: 60324

GnomAD4 genome AF: 0.00892 AC: 1359 AN: 152286 Hom.: 6 Cov.: 33 AF XY: 0.00843 AC XY: 628 AN XY: 74478

African (AFR) AF: 0.00253 AC: 105 AN: 41544

American (AMR) AF: 0.00797 AC: 122 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0154 AC: 74 AN: 4816

European-Finnish (FIN) AF: 0.00273 AC: 29 AN: 10630

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0141 AC: 957 AN: 68022

Other (OTH) AF: 0.0123 AC: 26 AN: 2108

Alfa AF: 0.0109 Hom.: 3

Bravo AF: 0.00900

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Benign	0.59
PhyloP100		1.1
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: rs76315093; hg19: chr20-45354973;