rs352783

Variant names:

• chr8-15749302-G-A
• rs352783
• NM_006765.4:c.1028+837G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006765.4(TUSC3):​c.1028+837G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,830 control chromosomes in the GnomAD database, including 8,357 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (8357 hom., cov: 30)
• Consequence: TUSC3 NM_006765.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.877

Genes affected

TUSC3 (HGNC:30242): (tumor suppressor candidate 3) This gene encodes a protein that has been associated with several biological functions including cellular magnesium uptake, protein glycosylation and embryonic development. This protein localizes to the endoplasmic reticulum and acts as a component of the oligosaccharyl transferase complex which is responsible for N-linked protein glycosylation. This gene is a candidate tumor suppressor gene. Homozygous mutations in this gene are associated with autosomal recessive nonsyndromic mental retardation-7 and in the proliferation and invasiveness of several cancers including metastatic pancreatic cancer, ovarian cancer and glioblastoma multiform. [provided by RefSeq, Oct 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUSC3	NM_006765.4	c.1028+837G>A		intron_variant	Intron 9 of 10	ENST00000503731.6	NP_006756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUSC3	ENST00000503731.6	c.1028+837G>A		intron_variant	Intron 9 of 10	1	NM_006765.4	ENSP00000424544.1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49498 AN: 151712 Hom.: 8335 Cov.: 30

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.308

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.326 AC: 49553 AN: 151830 Hom.: 8357 Cov.: 30 AF XY: 0.326 AC XY: 24165 AN XY: 74192

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.312

Alfa AF: 0.336 Hom.: 1401

Bravo AF: 0.337

Asia WGS AF: 0.242 AC: 838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.4
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs352783; hg19: chr8-15606811;