chr20-46709722-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_030777.4(SLC2A10):c.-15C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,545,498 control chromosomes in the GnomAD database, including 7 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 0.0017 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 5 hom. )

Consequence

SLC2A10
NM_030777.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: -0.0900

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 20-46709722-C-T is Benign according to our data. Variant chr20-46709722-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 139185.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00167 (255/152242) while in subpopulation AMR AF = 0.00287 (44/15306). AF 95% confidence interval is 0.0022. There are 2 homozygotes in GnomAd4. There are 115 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 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.-15C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_110404.1	O95528
	SLC2A10	NM_030777.4	MANE Select	c.-15C>T		5_prime_UTR	Exon 1 of 5	NP_110404.1	O95528

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC2A10	ENST00000359271.4	TSL:1 MANE Select	c.-15C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000352216.2	O95528
SLC2A10	ENST00000359271.4	TSL:1 MANE Select	c.-15C>T	5_prime_UTR	Exon 1 of 5	ENSP00000352216.2	O95528
SLC2A10	ENST00000862794.1		c.-15C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000532853.1

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

255

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.00243

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00135

AC:

184

AN:

136752

AF XY:

0.00135

show subpopulations

Gnomad AFR exome

AF:

0.000535

Gnomad AMR exome

AF:

0.00224

Gnomad ASJ exome

AF:

0.000125

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000659

Gnomad NFE exome

AF:

0.00223

Gnomad OTH exome

AF:

0.00273

GnomAD4 exome

AF:

0.00182

AC:

2541

AN:

1393256

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

1215

AN XY:

687248

show subpopulations

African (AFR)

AF:

0.000453

AC:

AN:

30894

American (AMR)

AF:

0.00262

AC:

AN:

35564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25022

East Asian (EAS)

AF:

0.00

AC:

AN:

35376

South Asian (SAS)

AF:

0.000380

AC:

AN:

78878

European-Finnish (FIN)

AF:

0.0000839

AC:

AN:

47688

Middle Eastern (MID)

AF:

0.00813

AC:

AN:

4552

European-Non Finnish (NFE)

AF:

0.00209

AC:

2248

AN:

1077574

Other (OTH)

AF:

0.00199

AC:

115

AN:

57708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

141

282

422

563

704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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:

0.00167

AC:

255

AN:

152242

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

115

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.000626

AC:

AN:

41548

American (AMR)

AF:

0.00287

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00243

AC:

165

AN:

67988

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00154

Hom.:

Bravo

AF:

0.00185

Asia WGS

AF:

0.000579

AC:

AN:

3470

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Arterial tortuosity syndrome (1)

Familial thoracic aortic aneurysm and aortic dissection (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.1

(source)

DANN

Benign

0.96

PhyloP100

-0.090

PromoterAI

-0.074

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=299/1

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