chr8-15755761-T-C

Position:

• chr8-15755761-T-C

Variant summary

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

The NM_006765.4(TUSC3):​c.1029-2030T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,112 control chromosomes in the GnomAD database, including 1,960 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 0.11 (1960 hom., cov: 32)
• Consequence: TUSC3 NM_006765.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUSC3	NM_006765.4	c.1029-2030T>C		intron_variant		ENST00000503731.6	NP_006756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUSC3	ENST00000503731.6	c.1029-2030T>C		intron_variant		1	NM_006765.4	ENSP00000424544	A1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16562 AN: 151994 Hom.: 1947 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0562

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0439

Gnomad FIN AF: 0.0131

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0322

Gnomad OTH AF: 0.0900

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

GnomAD4 genome AF: 0.109 AC: 16610 AN: 152112 Hom.: 1960 Cov.: 32 AF XY: 0.106 AC XY: 7857 AN XY: 74394

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.0560

Gnomad4 ASJ AF: 0.0294

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.0446

Gnomad4 FIN AF: 0.0131

Gnomad4 NFE AF: 0.0322

Gnomad4 OTH AF: 0.0890

Alfa AF: 0.0435 Hom.: 339

Bravo AF: 0.120

Asia WGS AF: 0.0960 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.6
DANN	Benign	0.71

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: rs352796; hg19: chr8-15613270;