rs240657

Variant names:

• chr8-15808103-G-A
• rs240657
• NM_001413679.1:c.*1451G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-15808103-G-A
• chr8-15808103-G-C
• chr8-15808103-G-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.*1451G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 152,206 control chromosomes in the GnomAD database, including 59,681 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 0.88 (59681 hom., cov: 32)
• Consequence: TUSC3 NM_001413679.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.562
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUSC3	NM_001413679.1	c.*1451G>A		3_prime_UTR_variant	Exon 9 of 9		NP_001400608.1
TUSC3	NM_001413684.1	c.*1584G>A		3_prime_UTR_variant	Exon 10 of 10		NP_001400613.1
TUSC3	NM_001413685.1	c.938-43421G>A		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: 0.885 AC: 134554 AN: 152086 Hom.: 59638 Cov.: 32

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.946

Gnomad MID AF: 0.841

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.873

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

GnomAD4 genome AF: 0.885 AC: 134647 AN: 152206 Hom.: 59681 Cov.: 32 AF XY: 0.882 AC XY: 65649 AN XY: 74416

African (AFR) AF: 0.922 AC: 38284 AN: 41532

American (AMR) AF: 0.804 AC: 12279 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2866 AN: 3472

East Asian (EAS) AF: 0.787 AC: 4064 AN: 5166

South Asian (SAS) AF: 0.854 AC: 4127 AN: 4830

European-Finnish (FIN) AF: 0.946 AC: 10019 AN: 10594

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.885 AC: 60201 AN: 68016

Other (OTH) AF: 0.866 AC: 1833 AN: 2116

Alfa AF: 0.880 Hom.: 156772

Bravo AF: 0.878

Asia WGS AF: 0.809 AC: 2814 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.25
PhyloP100		-0.56

Splicing

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

Other links and lift over

dbSNP: rs240657; hg19: chr8-15665612;