Genetic Variant SLC2A10:c.1288+10G>A (chr20-46726334-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 1.14

Publications

1 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 -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 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	O95528

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC2A10	ENST00000359271.4	TSL:1 MANE Select	c.1288+10G>A	intron	N/A	ENSP00000352216.2	O95528
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.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0143

AC XY:

10350

AN XY:

723216

show subpopulations

African (AFR)

AF:

0.00248

AC:

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:

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:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0158

AC:

17573

AN:

1111920

Other (OTH)

AF:

0.0121

AC:

728

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

1192

2384

3576

4768

5960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

686

1372

2058

2744

3430

<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:

0.00892

AC:

1359

AN:

152286

Hom.:

Cov.:

AF XY:

0.00843

AC XY:

628

AN XY:

74478

show subpopulations

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:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.0154

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00273

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0141

AC:

957

AN:

68022

Other (OTH)

AF:

0.0123

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

134

202

269

336

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:

0.0109

Hom.:

Bravo

AF:

0.00900

Asia WGS

AF:

0.00549

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 (5)

Familial thoracic aortic aneurysm and aortic dissection (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.59

PhyloP100

1.1

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

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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