chr12-7924406-C-T

Variant names:

• chr12-7924406-C-T
• rs3931701
• NM_006931.3:c.1068+4G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_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

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

ACMG classification

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 ClinVar 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	c.1068+4G>A		splice_region_variant, intron_variant	Intron 8 of 9	ENST00000075120.12	NP_008862.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0536 AC: 8042 AN: 150084 Hom.: 552 Cov.: 28

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

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.: 31 AF XY: 0.00626 AC XY: 4506 AN XY: 719504

⚠️ 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: 41 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: 50 AN: 53212

Middle Eastern (MID) AF: 0.00369 AC: 21 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.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0536 AC: 8049 AN: 150200 Hom.: 552 Cov.: 28 AF XY: 0.0537 AC XY: 3940 AN XY: 73384

⚠️ 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: 10 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: 19 AN: 10590

Middle Eastern (MID) AF: 0.0172 AC: 5 AN: 290

European-Non Finnish (NFE) AF: 0.00190 AC: 129 AN: 67948

Other (OTH) AF: 0.0422 AC: 88 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.

Alfa AF: 0.0246 Hom.: 46

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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
DANN	Benign	0.64
PhyloP100		0.86
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3931701; hg19: chr12-8077002; COSMIC: COSV50008746; COSMIC: COSV50008746;