8-15732502-A-G

Position:

• chr8-15732502-A-G

Variant summary

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

The NM_006765.4(TUSC3):​c.862+1773A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,916 control chromosomes in the GnomAD database, including 20,992 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 0.50 (20992 hom., cov: 31)
• Consequence: TUSC3 NM_006765.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.696

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUSC3	NM_006765.4	c.862+1773A>G		intron_variant		ENST00000503731.6	NP_006756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUSC3	ENST00000503731.6	c.862+1773A>G		intron_variant		1	NM_006765.4	ENSP00000424544	A1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76576 AN: 151798 Hom.: 20980 Cov.: 31

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.504 AC: 76606 AN: 151916 Hom.: 20992 Cov.: 31 AF XY: 0.507 AC XY: 37635 AN XY: 74238

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.521

Alfa AF: 0.571 Hom.: 32429

Bravo AF: 0.489

Asia WGS AF: 0.459 AC: 1597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.2
DANN	Benign	0.56

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: rs352750; hg19: chr8-15590011;