rs352780

Variant names:

• chr8-15783549-C-G
• rs352780
• NM_001413679.1:c.938-22814C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-15783549-C-G
• chr8-15783549-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001413679.1(TUSC3):​c.938-22814C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 151,780 control chromosomes in the GnomAD database, including 4,105 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 0.22 (4105 hom., cov: 32)
• Consequence: TUSC3 NM_001413679.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal recessive 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUSC3	NM_001413679.1	c.938-22814C>G		intron_variant	Intron 8 of 8		NP_001400608.1
TUSC3	NM_001413684.1	c.1029-22814C>G		intron_variant	Intron 9 of 9		NP_001400613.1
TUSC3	NM_001413685.1	c.937+39937C>G		intron_variant	Intron 8 of 8		NP_001400614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33777 AN: 151664 Hom.: 4084 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.223 AC: 33818 AN: 151780 Hom.: 4105 Cov.: 32 AF XY: 0.222 AC XY: 16499 AN XY: 74182

African (AFR) AF: 0.165 AC: 6846 AN: 41388

American (AMR) AF: 0.364 AC: 5538 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 968 AN: 3456

East Asian (EAS) AF: 0.287 AC: 1478 AN: 5148

South Asian (SAS) AF: 0.153 AC: 734 AN: 4812

European-Finnish (FIN) AF: 0.157 AC: 1655 AN: 10572

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.234 AC: 15909 AN: 67864

Other (OTH) AF: 0.236 AC: 497 AN: 2106

Alfa AF: 0.224 Hom.: 504

Bravo AF: 0.237

Asia WGS AF: 0.230 AC: 797 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.56
PhyloP100		-0.25

Splicing

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

Other links and lift over

dbSNP: rs352780; hg19: chr8-15641058; COSMIC: COSV56061300;