8-15844906-C-T

Variant names:

• chr8-15844906-C-T
• rs2736010
• NM_001413685.1:c.938-6618C>T

Variant summary

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

The NM_001413685.1(TUSC3):​c.938-6618C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,962 control chromosomes in the GnomAD database, including 17,663 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 0.46 (17663 hom., cov: 32)
• Consequence: TUSC3 NM_001413685.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 4 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUSC3	NM_001413685.1	c.938-6618C>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: 0.461 AC: 70005 AN: 151844 Hom.: 17672 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.461 AC: 69989 AN: 151962 Hom.: 17663 Cov.: 32 AF XY: 0.457 AC XY: 33948 AN XY: 74264

African (AFR) AF: 0.283 AC: 11715 AN: 41430

American (AMR) AF: 0.400 AC: 6100 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1607 AN: 3466

East Asian (EAS) AF: 0.222 AC: 1142 AN: 5140

South Asian (SAS) AF: 0.382 AC: 1839 AN: 4814

European-Finnish (FIN) AF: 0.630 AC: 6655 AN: 10556

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39296 AN: 67976

Other (OTH) AF: 0.482 AC: 1016 AN: 2108

Alfa AF: 0.432 Hom.: 2249

Bravo AF: 0.437

Asia WGS AF: 0.295 AC: 1026 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.50
PhyloP100		0.079

Splicing

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

Other links and lift over

dbSNP: rs2736010; hg19: chr8-15702415;