8-15800821-C-T

Variant names:

• chr8-15800821-C-T
• rs2721243
• NM_001413679.1:c.938-5542C>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.938-5542C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 152,122 control chromosomes in the GnomAD database, including 513 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 0.067 (513 hom., cov: 32)
• Consequence: TUSC3 NM_001413679.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUSC3	NM_001413679.1	c.938-5542C>T		intron_variant	Intron 8 of 8		NP_001400608.1
TUSC3	NM_001413684.1	c.1029-5542C>T		intron_variant	Intron 9 of 9		NP_001400613.1
TUSC3	NM_001413685.1	c.938-50703C>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: 0.0671 AC: 10195 AN: 152004 Hom.: 513 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0427

Gnomad ASJ AF: 0.0900

Gnomad EAS AF: 0.0683

Gnomad SAS AF: 0.0518

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0375

Gnomad OTH AF: 0.0645

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

GnomAD4 genome AF: 0.0671 AC: 10210 AN: 152122 Hom.: 513 Cov.: 32 AF XY: 0.0659 AC XY: 4899 AN XY: 74374

African (AFR) AF: 0.137 AC: 5703 AN: 41496

American (AMR) AF: 0.0426 AC: 651 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0900 AC: 312 AN: 3466

East Asian (EAS) AF: 0.0685 AC: 353 AN: 5156

South Asian (SAS) AF: 0.0527 AC: 254 AN: 4822

European-Finnish (FIN) AF: 0.0214 AC: 227 AN: 10588

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0375 AC: 2553 AN: 67992

Other (OTH) AF: 0.0652 AC: 138 AN: 2116

Alfa AF: 0.0511 Hom.: 516

Bravo AF: 0.0711

Asia WGS AF: 0.0680 AC: 239 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	0.75
DANN	Benign	0.70
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs2721243; hg19: chr8-15658330;