8-15535871-T-C

Variant names:

• chr8-15535871-T-C
• rs10110189
• NM_001413670.1:c.79-87209T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001413670.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUSC3	NM_001413670.1		c.79-87209T>C		intron	N/A	NP_001400599.1
	TUSC3	NM_001413671.1		c.-30-87209T>C		intron	N/A	NP_001400600.1
	TUSC3	NM_001413669.1		c.-30-87209T>C		intron	N/A	NP_001400598.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUSC3	ENST00000503191.5	TSL:3	n.189+52388T>C		intron	N/A

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

African (AFR) AF: 0.700 AC: 29016 AN: 41474

American (AMR) AF: 0.883 AC: 13506 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 3028 AN: 3472

East Asian (EAS) AF: 0.872 AC: 4509 AN: 5168

South Asian (SAS) AF: 0.661 AC: 3187 AN: 4818

European-Finnish (FIN) AF: 0.952 AC: 10093 AN: 10602

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.904 AC: 61515 AN: 68022

Other (OTH) AF: 0.854 AC: 1802 AN: 2110

Alfa AF: 0.870 Hom.: 23695

Bravo AF: 0.833

Asia WGS AF: 0.777 AC: 2700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.35
DANN	Benign	0.12
PhyloP100		-2.0

Splicing

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

Other links and lift over

dbSNP: rs10110189; hg19: chr8-15393380;