8-15535871-T-C

Variant summary

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

The NM_001413670.1(TUSC3):c.79-87209T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 152,162 control chromosomes in the GnomAD database, including 54,280 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 0.84 (54280 hom., cov: 31)
• Consequence: TUSC3 NM_001413670.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUSC3	NM_001413669.1	c.-30-87209T>C		intron_variant
TUSC3	NM_001413670.1	c.79-87209T>C		intron_variant
TUSC3	NM_001413671.1	c.-30-87209T>C		intron_variant
TUSC3	NM_001413672.1	c.-31+52388T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUSC3	ENST00000503191.5	n.189+52388T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127553 AN: 152044 Hom.: 54254 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.812

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.952

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.853

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

GnomAD4 genome AF: 0.839 AC: 127631 AN: 152162 Hom.: 54280 Cov.: 31 AF XY: 0.839 AC XY: 62449 AN XY: 74394

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.883

Gnomad4 ASJ AF: 0.872

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.952

Gnomad4 NFE AF: 0.904

Gnomad4 OTH AF: 0.854

Alfa AF: 0.862 Hom.: 5863

Bravo AF: 0.833

Asia WGS AF: 0.777 AC: 2700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.35
Dann	Benign	0.12

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10110189; hg19: chr8-15393380;