12-7924406-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_006931.3(SLC2A3):c.1068+4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 552 hom., cov: 28)

Exomes 𝑓: 0.0060 ( 722 hom. )

Failed GnomAD Quality Control

Consequence

SLC2A3
NM_006931.3 splice_region, intron

Scores

Splicing: ADA: 0.00006109

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.860

Publications

5 publications found

Variant links:

Genes affected

SLC2A3 (HGNC:11007): (solute carrier family 2 member 3) Enables dehydroascorbic acid transmembrane transporter activity; glucose binding activity; and glucose transmembrane transporter activity. Involved in glucose import across plasma membrane and transport across blood-brain barrier. Is integral component of plasma membrane. Biomarker of Alzheimer's disease; acanthosis nigricans; diabetes mellitus; and type 2 diabetes mellitus. [provided by Alliance of Genome Resources, Apr 2022]

SLC2A3 Gene-Disease associations (from GenCC):

Huntington disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SLC2A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 12-7924406-C-T is Benign according to our data. Variant chr12-7924406-C-T is described in CliVar as Benign. Clinvar id is 771454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-7924406-C-T is described in CliVar as Benign. Clinvar id is 771454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-7924406-C-T is described in CliVar as Benign. Clinvar id is 771454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-7924406-C-T is described in CliVar as Benign. Clinvar id is 771454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-7924406-C-T is described in CliVar as Benign. Clinvar id is 771454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-7924406-C-T is described in CliVar as Benign. Clinvar id is 771454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A3	NM_006931.3 link	c.1068+4G>A		splice_region_variant, intron_variant	Intron 8 of 9	ENST00000075120.12	NP_008862.1	P11169

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A3	ENST00000075120.12 link	c.1068+4G>A		splice_region_variant, intron_variant	Intron 8 of 9	1	NM_006931.3	ENSP00000075120.7		P11169

Frequencies

GnomAD3 genomes

AF:

0.0536

AC:

8042

AN:

150084

Hom.:

552

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0542

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.0569

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.0160

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.0421

GnomAD2 exomes

AF:

0.0118

AC:

2906

AN:

245340

AF XY:

0.0105

show subpopulations

Gnomad AFR exome

AF:

0.0429

Gnomad AMR exome

AF:

0.0166

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.0811

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.000335

Gnomad OTH exome

AF:

0.00912

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00602

AC:

8714

AN:

1446656

Hom.:

722

Cov.:

AF XY:

0.00626

AC XY:

4506

AN XY:

719504

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0502

AC:

1526

AN:

30376

American (AMR)

AF:

0.0194

AC:

827

AN:

42638

Ashkenazi Jewish (ASJ)

AF:

0.00158

AC:

AN:

26030

East Asian (EAS)

AF:

0.107

AC:

3851

AN:

35892

South Asian (SAS)

AF:

0.0152

AC:

1269

AN:

83402

European-Finnish (FIN)

AF:

0.000940

AC:

AN:

53212

Middle Eastern (MID)

AF:

0.00369

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.000392

AC:

435

AN:

1110266

Other (OTH)

AF:

0.0117

AC:

694

AN:

59146

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.306

Heterozygous variant carriers

487

975

1462

1950

2437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0536

AC:

8049

AN:

150200

Hom.:

552

Cov.:

AF XY:

0.0537

AC XY:

3940

AN XY:

73384

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.142

AC:

5708

AN:

40218

American (AMR)

AF:

0.0541

AC:

816

AN:

15076

Ashkenazi Jewish (ASJ)

AF:

0.00289

AC:

AN:

3466

East Asian (EAS)

AF:

0.207

AC:

1009

AN:

4880

South Asian (SAS)

AF:

0.0559

AC:

265

AN:

4738

European-Finnish (FIN)

AF:

0.00179

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.0172

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00190

AC:

129

AN:

67948

Other (OTH)

AF:

0.0422

AC:

AN:

2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.370

Heterozygous variant carriers

310

620

930

1240

1550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0246

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.5

(source)

DANN

Benign

0.64

PhyloP100

0.86

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000061

dbscSNV1_RF

Benign

0.086

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over