20-46725352-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBS1BS2

The NM_030777.4(SLC2A10):c.316G>T(p.Ala106Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,614,082 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A106G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0080 ( 20 hom., cov: 33)

Exomes 𝑓: 0.00084 ( 19 hom. )

Consequence

SLC2A10
NM_030777.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.380

Publications

8 publications found

Variant links:

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, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, G2P

SLC2A10 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_030777.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

PM1

In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 7 uncertain in NM_030777.4

BP4

Computational evidence support a benign effect (MetaRNN=0.004226029).

BP6

Variant 20-46725352-G-T is Benign according to our data. Variant chr20-46725352-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 139170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00805 (1226/152334) while in subpopulation AFR AF = 0.0279 (1162/41584). AF 95% confidence interval is 0.0266. There are 20 homozygotes in GnomAd4. There are 570 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 20 AR 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.316G>T	p.Ala106Ser	missense	Exon 2 of 5	NP_110404.1	O95528

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC2A10	ENST00000359271.4	TSL:1 MANE Select	c.316G>T	p.Ala106Ser	missense	Exon 2 of 5	ENSP00000352216.2	O95528
SLC2A10	ENST00000862794.1		c.610G>T	p.Ala204Ser	missense	Exon 2 of 5	ENSP00000532853.1
SLC2A10	ENST00000862792.1		c.316G>T	p.Ala106Ser	missense	Exon 2 of 6	ENSP00000532851.1

Frequencies

GnomAD3 genomes

AF:

0.00803

AC:

1223

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0280

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00226

AC:

566

AN:

250830

AF XY:

0.00173

show subpopulations

Gnomad AFR exome

AF:

0.0308

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000843

AC:

1232

AN:

1461748

Hom.:

Cov.:

AF XY:

0.000710

AC XY:

516

AN XY:

727178

show subpopulations

African (AFR)

AF:

0.0301

AC:

1007

AN:

33480

American (AMR)

AF:

0.00186

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53280

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000378

AC:

AN:

1112010

Other (OTH)

AF:

0.00157

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

184

276

368

460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00805

AC:

1226

AN:

152334

Hom.:

Cov.:

AF XY:

0.00765

AC XY:

570

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0279

AC:

1162

AN:

41584

American (AMR)

AF:

0.00300

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68034

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

124

187

249

311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00235

Hom.:

Bravo

AF:

0.00949

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Arterial tortuosity syndrome (5)

not specified (3)

Familial thoracic aortic aneurysm and aortic dissection (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.10

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.18

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.048

MetaRNN

Benign

0.0042

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.0

PhyloP100

-0.38

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.99

REVEL

Benign

0.17

Sift

Benign

0.29

Sift4G

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.055

gMVP

0.12

Mutation Taster

=100/0

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over