NM_001413679.1:c.938-4243G>A

Variant names:

• chr8-15802120-G-A
• rs6530906
• NM_001413679.1:c.938-4243G>A

Variant summary

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

The NM_001413679.1(TUSC3):​c.938-4243G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,068 control chromosomes in the GnomAD database, including 49,349 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 0.81 (49349 hom., cov: 31)
• Consequence: TUSC3 NM_001413679.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 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.938-4243G>A		intron	N/A	NP_001400608.1
	TUSC3	NM_001413684.1		c.1029-4243G>A		intron	N/A	NP_001400613.1
	TUSC3	NM_001413685.1		c.938-49404G>A		intron	N/A	NP_001400614.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122344 AN: 151950 Hom.: 49296 Cov.: 31

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.818

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

GnomAD4 genome AF: 0.805 AC: 122455 AN: 152068 Hom.: 49349 Cov.: 31 AF XY: 0.804 AC XY: 59717 AN XY: 74302

African (AFR) AF: 0.772 AC: 32041 AN: 41484

American (AMR) AF: 0.804 AC: 12283 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2851 AN: 3472

East Asian (EAS) AF: 0.842 AC: 4316 AN: 5128

South Asian (SAS) AF: 0.813 AC: 3920 AN: 4822

European-Finnish (FIN) AF: 0.769 AC: 8132 AN: 10574

Middle Eastern (MID) AF: 0.771 AC: 225 AN: 292

European-Non Finnish (NFE) AF: 0.827 AC: 56266 AN: 67996

Other (OTH) AF: 0.820 AC: 1730 AN: 2110

Alfa AF: 0.800 Hom.: 4721

Bravo AF: 0.805

Asia WGS AF: 0.815 AC: 2836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0050
DANN	Benign	0.65
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs6530906; hg19: chr8-15659629;