chr8-15732502-A-G

Variant names:

• chr8-15732502-A-G
• rs352750
• NM_006765.4:c.862+1773A>G

Variant summary

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

The NM_001413675.1(TUSC3):​c.*1666A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,916 control chromosomes in the GnomAD database, including 20,992 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 0.50 (20992 hom., cov: 31)
• Consequence: TUSC3 NM_001413675.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.696
• Publications: 7 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: Labcorp Genetics (formerly Invitae), G2P
• 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 (NFE) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001413675.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUSC3	NM_006765.4	MANE Select	c.862+1773A>G		intron	N/A	NP_006756.2
	TUSC3	NM_001413675.1		c.*1666A>G		3_prime_UTR	Exon 7 of 7	NP_001400604.1
	TUSC3	NM_001413679.1		c.862+1773A>G		intron	N/A	NP_001400608.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUSC3	ENST00000503731.6	TSL:1 MANE Select	c.862+1773A>G		intron	N/A	ENSP00000424544.1	Q13454-1
	TUSC3	ENST00000382020.8	TSL:1	c.862+1773A>G		intron	N/A	ENSP00000371450.4	Q13454-2
	TUSC3	ENST00000947282.1		c.937+1773A>G		intron	N/A	ENSP00000617341.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76576 AN: 151798 Hom.: 20980 Cov.: 31

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.504 AC: 76606 AN: 151916 Hom.: 20992 Cov.: 31 AF XY: 0.507 AC XY: 37635 AN XY: 74238

African (AFR) AF: 0.281 AC: 11659 AN: 41424

American (AMR) AF: 0.572 AC: 8721 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1997 AN: 3472

East Asian (EAS) AF: 0.558 AC: 2871 AN: 5146

South Asian (SAS) AF: 0.335 AC: 1613 AN: 4818

European-Finnish (FIN) AF: 0.682 AC: 7198 AN: 10550

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40909 AN: 67950

Other (OTH) AF: 0.521 AC: 1100 AN: 2110

Alfa AF: 0.563 Hom.: 40517

Bravo AF: 0.489

Asia WGS AF: 0.459 AC: 1597 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	4.2
DANN	Benign	0.56
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs352750; hg19: chr8-15590011;