Genetic Variant NM_030777.4:c.1541A>G (chr20-46729482-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_030777.4(SLC2A10):c.1541A>G(p.Lys514Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,614,048 control chromosomes in the GnomAD database, including 1,571 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. K514K) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.058 ( 849 hom., cov: 31)

Exomes 𝑓: 0.0061 ( 722 hom. )

Consequence

SLC2A10
NM_030777.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.819

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

SLC2A10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021744668).

BP6

Variant 20-46729482-A-G is Benign according to our data. Variant chr20-46729482-A-G is described in ClinVar as Benign. ClinVar VariationId is 139177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

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.1541A>G	p.Lys514Arg	missense	Exon 4 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.1541A>G	p.Lys514Arg	missense	Exon 4 of 5	ENSP00000352216.2	O95528
SLC2A10	ENST00000862794.1		c.1835A>G	p.Lys612Arg	missense	Exon 4 of 5	ENSP00000532853.1
SLC2A10	ENST00000862792.1		c.1673A>G	p.Lys558Arg	missense	Exon 5 of 6	ENSP00000532851.1

Frequencies

GnomAD3 genomes

AF:

0.0576

AC:

8764

AN:

152112

Hom.:

849

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0198

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.000970

Gnomad OTH

AF:

0.0426

GnomAD2 exomes

AF:

0.0152

AC:

3818

AN:

251424

AF XY:

0.0109

show subpopulations

Gnomad AFR exome

AF:

0.206

Gnomad AMR exome

AF:

0.00945

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000897

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00613

AC:

8957

AN:

1461818

Hom.:

722

Cov.:

AF XY:

0.00526

AC XY:

3823

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.206

AC:

6899

AN:

33476

American (AMR)

AF:

0.0108

AC:

483

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000325

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.0109

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000621

AC:

690

AN:

1111958

Other (OTH)

AF:

0.0131

AC:

793

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

434

868

1303

1737

2171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

220

440

660

880

1100

<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:

0.0576

AC:

8769

AN:

152230

Hom.:

849

Cov.:

AF XY:

0.0564

AC XY:

4200

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.200

AC:

8300

AN:

41488

American (AMR)

AF:

0.0198

AC:

303

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000970

AC:

AN:

68028

Other (OTH)

AF:

0.0421

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

354

707

1061

1414

1768

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.0226

Hom.:

737

Bravo

AF:

0.0656

ESP6500AA

AF:

0.192

AC:

846

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.0186

AC:

2263

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.00154

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Arterial tortuosity syndrome (3)

Familial thoracic aortic aneurysm and aortic dissection (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

1.0

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.099

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.17

PhyloP100

-0.82

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.69

REVEL

Benign

0.19

Sift

Benign

0.30

Sift4G

Benign

0.66

Polyphen

0.0

Vest4

0.040

MPC

0.055

ClinPred

0.0020

GERP RS

-2.5

Varity_R

0.049

gMVP

0.45

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

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