rs1908465

Positions:

• chr8-15450924-T-A
• chr8-15450924-T-G

Variant summary

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

The NM_001413670.1(TUSC3):​c.78+28004T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 151,984 control chromosomes in the GnomAD database, including 39,690 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 0.72 (39690 hom., cov: 31)
• Consequence: TUSC3 NM_001413670.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

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]

TUSC3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUSC3	NM_001413670.1	c.78+28004T>A		intron_variant			NP_001400599.1
TUSC3	NM_001413671.1	c.-31+33619T>A		intron_variant			NP_001400600.1
TUSC3	NM_001413669.1	c.-31+33619T>A		intron_variant			NP_001400598.1
TUSC3	NM_001413672.1	c.-128-32462T>A		intron_variant			NP_001400601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUSC3	ENST00000503191.5	n.92-32462T>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109509 AN: 151870 Hom.: 39661 Cov.: 31

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.721 AC: 109589 AN: 151984 Hom.: 39690 Cov.: 31 AF XY: 0.725 AC XY: 53877 AN XY: 74280

Gnomad4 AFR AF: 0.698

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.886

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.719

Alfa AF: 0.721 Hom.: 4702

Bravo AF: 0.719

Asia WGS AF: 0.797 AC: 2770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.0
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1908465; hg19: chr8-15308433;