8-15468159-T-G

Variant names:

• chr8-15468159-T-G
• rs2172820
• NM_001413670.1:c.78+45239T>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+45239T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,136 control chromosomes in the GnomAD database, including 4,994 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 0.25 (4994 hom., cov: 32)
• Consequence: TUSC3 NM_001413670.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUSC3	NM_001413670.1	c.78+45239T>G		intron_variant	Intron 2 of 10		NP_001400599.1
TUSC3	NM_001413671.1	c.-31+50854T>G		intron_variant	Intron 1 of 10		NP_001400600.1
TUSC3	NM_001413669.1	c.-31+50854T>G		intron_variant	Intron 1 of 9		NP_001400598.1
TUSC3	NM_001413672.1	c.-128-15227T>G		intron_variant	Intron 1 of 10		NP_001400601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUSC3	ENST00000503191.5	n.92-15227T>G		intron_variant	Intron 1 of 5	3

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38457 AN: 152018 Hom.: 4996 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.253 AC: 38474 AN: 152136 Hom.: 4994 Cov.: 32 AF XY: 0.250 AC XY: 18565 AN XY: 74362

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.278

Alfa AF: 0.261 Hom.: 4500

Bravo AF: 0.263

Asia WGS AF: 0.227 AC: 790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.1
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2172820; hg19: chr8-15325668;