NM_006765.4:c.709-2679T>C

Variant names:

• chr8-15671068-T-C
• rs6530893
• NM_006765.4:c.709-2679T>C

Variant summary

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

The NM_006765.4(TUSC3):​c.709-2679T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 151,850 control chromosomes in the GnomAD database, including 3,057 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 0.14 (3057 hom., cov: 32)
• Consequence: TUSC3 NM_006765.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUSC3	NM_006765.4	c.709-2679T>C		intron_variant	Intron 5 of 10	ENST00000503731.6	NP_006756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUSC3	ENST00000503731.6	c.709-2679T>C		intron_variant	Intron 5 of 10	1	NM_006765.4	ENSP00000424544.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20936 AN: 151730 Hom.: 3042 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0797

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.0836

Gnomad FIN AF: 0.0933

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.138 AC: 21001 AN: 151850 Hom.: 3057 Cov.: 32 AF XY: 0.139 AC XY: 10311 AN XY: 74196

African (AFR) AF: 0.367 AC: 15213 AN: 41424

American (AMR) AF: 0.0795 AC: 1209 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.0697 AC: 242 AN: 3472

East Asian (EAS) AF: 0.166 AC: 852 AN: 5130

South Asian (SAS) AF: 0.0834 AC: 402 AN: 4818

European-Finnish (FIN) AF: 0.0933 AC: 990 AN: 10606

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0263 AC: 1785 AN: 67888

Other (OTH) AF: 0.123 AC: 259 AN: 2106

Alfa AF: 0.126 Hom.: 439

Bravo AF: 0.148

Asia WGS AF: 0.133 AC: 461 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.27
PhyloP100		1.1
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: rs6530893; hg19: chr8-15528577;