Variant 8-15540311-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006765.4(TUSC3):c.-120C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,323,854 control chromosomes in the GnomAD database, including 27,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3137 hom., cov: 32)

Exomes 𝑓: 0.20 ( 24627 hom. )

Consequence

TUSC3
NM_006765.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.162

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 8-15540311-C-T is Benign according to our data. Variant chr8-15540311-C-T is described in ClinVar as [Benign]. Clinvar id is 362304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUSC3	NM_006765.4 linkuse as main transcript	c.-120C>T		5_prime_UTR_variant	1/11	ENST00000503731.6	NP_006756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUSC3	ENST00000503731.6 linkuse as main transcript	c.-120C>T		5_prime_UTR_variant	1/11	1	NM_006765.4	ENSP00000424544	A1	Q13454-1

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

30942

AN:

152042

Hom.:

3137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.235

Gnomad EAS

AF:

0.237

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.202

GnomAD4 exome

AF:

0.203

AC:

237953

AN:

1171696

Hom.:

24627

Cov.:

AF XY:

0.205

AC XY:

116100

AN XY:

566884

show subpopulations

Gnomad4 AFR exome

AF:

0.197

Gnomad4 AMR exome

AF:

0.222

Gnomad4 ASJ exome

AF:

0.240

Gnomad4 EAS exome

AF:

0.268

Gnomad4 SAS exome

AF:

0.267

Gnomad4 FIN exome

AF:

0.200

Gnomad4 NFE exome

AF:

0.197

Gnomad4 OTH exome

AF:

0.200

GnomAD4 genome

AF:

0.203

AC:

30951

AN:

152158

Hom.:

3137

Cov.:

AF XY:

0.205

AC XY:

15222

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.196

Gnomad4 AMR

AF:

0.205

Gnomad4 ASJ

AF:

0.235

Gnomad4 EAS

AF:

0.237

Gnomad4 SAS

AF:

0.265

Gnomad4 FIN

AF:

0.196

Gnomad4 NFE

AF:

0.200

Gnomad4 OTH

AF:

0.200

Alfa

AF:

0.103

Hom.:

148

Bravo

AF:

0.206

Asia WGS

AF:

0.219

AC:

760

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -

Congenital disorder of glycosylation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over