rs4831760

chr8-15675076-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.798+1240T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,824 control chromosomes in the GnomAD database, including 7,078 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 0.30 (7078 hom., cov: 31)
• Consequence: TUSC3 NM_006765.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUSC3	NM_006765.4	c.798+1240T>C		intron_variant		ENST00000503731.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUSC3	ENST00000503731.6	c.798+1240T>C		intron_variant		1	NM_006765.4	A1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45315 AN: 151708 Hom.: 7077 Cov.: 31

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.0866

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.299 AC: 45342 AN: 151824 Hom.: 7078 Cov.: 31 AF XY: 0.294 AC XY: 21796 AN XY: 74190

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.0862

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.283

Alfa AF: 0.288 Hom.: 8525

Bravo AF: 0.293

Asia WGS AF: 0.115 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	2.0
Dann	Benign	0.42

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: rs4831760; hg19: chr8-15532585;