chr8-15540240-C-T

Variant names:

• chr8-15540240-C-T
• rs886062765
• ENST00000382020.8:c.-191C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178234.2(TUSC3):​c.-191C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TUSC3 NM_178234.2 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.328
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178234.2. 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_178234.2		c.-191C>T		5_prime_UTR	Exon 1 of 10	NP_839952.1	Q13454-2
	TUSC3	NM_001413670.1		c.79-82840C>T		intron	N/A	NP_001400599.1
	TUSC3	NM_001413671.1		c.-30-82840C>T		intron	N/A	NP_001400600.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUSC3	ENST00000382020.8	TSL:1	c.-191C>T		5_prime_UTR	Exon 1 of 10	ENSP00000371450.4	Q13454-2
	TUSC3	ENST00000877722.1		c.-191C>T		5_prime_UTR	Exon 1 of 11	ENSP00000547781.1
	TUSC3	ENST00000928815.1		c.-191C>T		5_prime_UTR	Exon 1 of 10	ENSP00000598874.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 653996 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 324836

African (AFR) AF: 0.00 AC: 0 AN: 13398

American (AMR) AF: 0.00 AC: 0 AN: 7956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12394

East Asian (EAS) AF: 0.00 AC: 0 AN: 24150

South Asian (SAS) AF: 0.00 AC: 0 AN: 29568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2188

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 506876

Other (OTH) AF: 0.00 AC: 0 AN: 30542

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Benign	0.97
PhyloP100		-0.33
PromoterAI		0.90	Over-expression

Splicing

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

Other links and lift over

dbSNP: rs886062765; hg19: chr8-15397749;