8-15799187-T-G

Variant names:

• chr8-15799187-T-G
• rs2721207
• NM_001413679.1:c.938-7176T>G

Variant summary

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

The NM_001413679.1(TUSC3):​c.938-7176T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0416 in 152,182 control chromosomes in the GnomAD database, including 155 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 0.042 (155 hom., cov: 32)
• Consequence: TUSC3 NM_001413679.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0626 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001413679.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUSC3	NM_001413679.1		c.938-7176T>G		intron	N/A	NP_001400608.1
	TUSC3	NM_001413684.1		c.1029-7176T>G		intron	N/A	NP_001400613.1
	TUSC3	NM_001413685.1		c.938-52337T>G		intron	N/A	NP_001400614.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6311 AN: 152064 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.0582

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.0912

Gnomad EAS AF: 0.0497

Gnomad SAS AF: 0.0670

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0318

Gnomad OTH AF: 0.0460

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

GnomAD4 genome AF: 0.0416 AC: 6326 AN: 152182 Hom.: 155 Cov.: 32 AF XY: 0.0420 AC XY: 3122 AN XY: 74412

African (AFR) AF: 0.0582 AC: 2418 AN: 41546

American (AMR) AF: 0.0343 AC: 524 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0912 AC: 316 AN: 3466

East Asian (EAS) AF: 0.0495 AC: 255 AN: 5154

South Asian (SAS) AF: 0.0687 AC: 331 AN: 4816

European-Finnish (FIN) AF: 0.0190 AC: 202 AN: 10614

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0318 AC: 2164 AN: 67984

Other (OTH) AF: 0.0455 AC: 96 AN: 2108

Alfa AF: 0.0348 Hom.: 221

Bravo AF: 0.0425

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.52
DANN	Benign	0.63
PhyloP100		-0.87

Splicing

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

Other links and lift over

dbSNP: rs2721207; hg19: chr8-15656696;