rs1429087

Variant names:

• chr8-15543065-A-C
• rs1429087
• NM_006765.4:c.138+2497A>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.138+2497A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,058 control chromosomes in the GnomAD database, including 6,870 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 0.28 (6870 hom., cov: 32)
• Consequence: TUSC3 NM_006765.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 7 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 (AMR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUSC3	NM_006765.4	c.138+2497A>C		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.138+2497A>C		intron_variant	Intron 1 of 10	1	NM_006765.4	ENSP00000424544.1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43217 AN: 151938 Hom.: 6854 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.284 AC: 43259 AN: 152058 Hom.: 6870 Cov.: 32 AF XY: 0.283 AC XY: 21020 AN XY: 74322

African (AFR) AF: 0.163 AC: 6759 AN: 41502

American (AMR) AF: 0.355 AC: 5435 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1067 AN: 3464

East Asian (EAS) AF: 0.143 AC: 739 AN: 5170

South Asian (SAS) AF: 0.169 AC: 814 AN: 4820

European-Finnish (FIN) AF: 0.339 AC: 3588 AN: 10572

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23964 AN: 67928

Other (OTH) AF: 0.292 AC: 614 AN: 2106

Alfa AF: 0.326 Hom.: 12445

Bravo AF: 0.281

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.035
DANN	Benign	0.65
PhyloP100		-2.1
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: rs1429087; hg19: chr8-15400574;