rs6994908

Variant names:

• chr8-15674943-T-C
• rs6994908
• NM_006765.4:c.798+1107T>C

Variant summary

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

The NM_006765.4(TUSC3):​c.798+1107T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,826 control chromosomes in the GnomAD database, including 7,945 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 0.32 (7945 hom., cov: 32)
• Consequence: TUSC3 NM_006765.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUSC3	NM_006765.4	c.798+1107T>C		intron_variant	Intron 6 of 10	ENST00000503731.6	NP_006756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUSC3	ENST00000503731.6	c.798+1107T>C		intron_variant	Intron 6 of 10	1	NM_006765.4	ENSP00000424544.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48595 AN: 151708 Hom.: 7951 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.375

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.320 AC: 48609 AN: 151826 Hom.: 7945 Cov.: 32 AF XY: 0.320 AC XY: 23727 AN XY: 74158

African (AFR) AF: 0.312 AC: 12936 AN: 41422

American (AMR) AF: 0.254 AC: 3870 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 997 AN: 3466

East Asian (EAS) AF: 0.266 AC: 1371 AN: 5150

South Asian (SAS) AF: 0.219 AC: 1055 AN: 4814

European-Finnish (FIN) AF: 0.427 AC: 4495 AN: 10526

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.335 AC: 22762 AN: 67904

Other (OTH) AF: 0.328 AC: 691 AN: 2108

Alfa AF: 0.325 Hom.: 1007

Bravo AF: 0.309

Asia WGS AF: 0.235 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.48
DANN	Benign	0.52
PhyloP100		-1.9
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: rs6994908; hg19: chr8-15532452;