rs6530893

Positions:

• chr8-15671068-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.709-2679T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 151,850 control chromosomes in the GnomAD database, including 3,057 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 0.14 (3057 hom., cov: 32)
• Consequence: TUSC3 NM_006765.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUSC3	NM_006765.4	c.709-2679T>C		intron_variant		ENST00000503731.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUSC3	ENST00000503731.6	c.709-2679T>C		intron_variant		1	NM_006765.4	A1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20936 AN: 151730 Hom.: 3042 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0797

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.0836

Gnomad FIN AF: 0.0933

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.138 AC: 21001 AN: 151850 Hom.: 3057 Cov.: 32 AF XY: 0.139 AC XY: 10311 AN XY: 74196

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.0795

Gnomad4 ASJ AF: 0.0697

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.0834

Gnomad4 FIN AF: 0.0933

Gnomad4 NFE AF: 0.0263

Gnomad4 OTH AF: 0.123

Alfa AF: 0.118 Hom.: 382

Bravo AF: 0.148

Asia WGS AF: 0.133 AC: 461 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.27

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: rs6530893; hg19: chr8-15528577;