8-15784704-C-T

Variant names:

• chr8-15784704-C-T
• rs2604376
• NM_001413679.1:c.938-21659C>T

Variant summary

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

The NM_001413679.1(TUSC3):​c.938-21659C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 151,726 control chromosomes in the GnomAD database, including 12,634 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 0.39 (12634 hom., cov: 31)
• Consequence: TUSC3 NM_001413679.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87
• Publications: 5 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUSC3	NM_001413679.1	c.938-21659C>T		intron_variant	Intron 8 of 8		NP_001400608.1
TUSC3	NM_001413684.1	c.1029-21659C>T		intron_variant	Intron 9 of 9		NP_001400613.1
TUSC3	NM_001413685.1	c.937+41092C>T		intron_variant	Intron 8 of 8		NP_001400614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59550 AN: 151610 Hom.: 12597 Cov.: 31

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.393 AC: 59633 AN: 151726 Hom.: 12634 Cov.: 31 AF XY: 0.390 AC XY: 28927 AN XY: 74132

African (AFR) AF: 0.560 AC: 23175 AN: 41358

American (AMR) AF: 0.327 AC: 4981 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1245 AN: 3460

East Asian (EAS) AF: 0.466 AC: 2389 AN: 5128

South Asian (SAS) AF: 0.434 AC: 2083 AN: 4802

European-Finnish (FIN) AF: 0.250 AC: 2642 AN: 10548

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21920 AN: 67892

Other (OTH) AF: 0.374 AC: 787 AN: 2106

Alfa AF: 0.349 Hom.: 31510

Bravo AF: 0.405

Asia WGS AF: 0.431 AC: 1498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.34
PhyloP100		-2.9

Splicing

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

Other links and lift over

dbSNP: rs2604376; hg19: chr8-15642213;