8-15621057-C-T

Variant names:

• chr8-15621057-C-T
• rs10093881
• NM_006765.4:c.139-2023C>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.139-2023C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,774 control chromosomes in the GnomAD database, including 22,817 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 0.55 (22817 hom., cov: 31)
• Consequence: TUSC3 NM_006765.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUSC3	NM_006765.4	c.139-2023C>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.139-2023C>T		intron_variant	Intron 1 of 10	1	NM_006765.4	ENSP00000424544.1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 82942 AN: 151656 Hom.: 22796 Cov.: 31

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.547 AC: 83010 AN: 151774 Hom.: 22817 Cov.: 31 AF XY: 0.547 AC XY: 40544 AN XY: 74172

African (AFR) AF: 0.504 AC: 20858 AN: 41400

American (AMR) AF: 0.515 AC: 7853 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1981 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3082 AN: 5152

South Asian (SAS) AF: 0.510 AC: 2449 AN: 4806

European-Finnish (FIN) AF: 0.595 AC: 6243 AN: 10494

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38727 AN: 67894

Other (OTH) AF: 0.539 AC: 1138 AN: 2110

Alfa AF: 0.445 Hom.: 1275

Bravo AF: 0.543

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.99
DANN	Benign	0.77
PhyloP100		-0.34
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: rs10093881; hg19: chr8-15478566;