chr8-15621415-C-T

Variant names:

• chr8-15621415-C-T
• rs10094375
• NM_006765.4:c.139-1665C>T

Variant summary

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

The NM_006765.4(TUSC3):​c.139-1665C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 149,996 control chromosomes in the GnomAD database, including 53,296 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 (53296 hom., cov: 29)
• Consequence: TUSC3 NM_006765.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.578
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUSC3	NM_006765.4	c.139-1665C>T		intron_variant	Intron 1 of 10	ENST00000503731.6	NP_006756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUSC3	ENST00000503731.6	c.139-1665C>T		intron_variant	Intron 1 of 10	1	NM_006765.4	ENSP00000424544.1

Frequencies

GnomAD3 genomes AF: 0.841 AC: 126103 AN: 149938 Hom.: 53264 Cov.: 29

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.825

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

GnomAD4 genome AF: 0.841 AC: 126169 AN: 149996 Hom.: 53296 Cov.: 29 AF XY: 0.839 AC XY: 61431 AN XY: 73230

African (AFR) AF: 0.812 AC: 33397 AN: 41112

American (AMR) AF: 0.780 AC: 11689 AN: 14986

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2964 AN: 3466

East Asian (EAS) AF: 0.819 AC: 4204 AN: 5130

South Asian (SAS) AF: 0.674 AC: 3222 AN: 4782

European-Finnish (FIN) AF: 0.931 AC: 9009 AN: 9680

Middle Eastern (MID) AF: 0.776 AC: 222 AN: 286

European-Non Finnish (NFE) AF: 0.874 AC: 59042 AN: 67560

Other (OTH) AF: 0.826 AC: 1721 AN: 2084

Alfa AF: 0.851 Hom.: 9598

Bravo AF: 0.833

Asia WGS AF: 0.764 AC: 2621 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.4
DANN	Benign	0.35
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10094375; hg19: chr8-15478924;