Variant 8-15743653-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006765.4(TUSC3):c.937+41C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,599,688 control chromosomes in the GnomAD database, including 181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0098 ( 9 hom., cov: 33)

Exomes 𝑓: 0.011 ( 172 hom. )

Consequence

TUSC3
NM_006765.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.905

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:

TUSC3 (HGNC:):

TUSC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 8-15743653-C-G is Benign according to our data. Variant chr8-15743653-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1187727.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0098 (1491/152204) while in subpopulation SAS AF= 0.0249 (120/4810). AF 95% confidence interval is 0.0213. There are 9 homozygotes in gnomad4. There are 722 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUSC3	NM_006765.4 linkuse as main transcript	c.937+41C>G		intron_variant		ENST00000503731.6	NP_006756.2	Q13454-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUSC3	ENST00000503731.6 linkuse as main transcript	c.937+41C>G		intron_variant		1	NM_006765.4	ENSP00000424544.1		Q13454-1

Frequencies

GnomAD3 genomes

AF:

0.00980

AC:

1490

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00229

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.0372

Gnomad EAS

AF:

0.0191

Gnomad SAS

AF:

0.0247

Gnomad FIN

AF:

0.00689

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.0147

AC:

3675

AN:

249528

Hom.:

AF XY:

0.0164

AC XY:

2212

AN XY:

135034

show subpopulations

Gnomad AFR exome

AF:

0.00186

Gnomad AMR exome

AF:

0.00756

Gnomad ASJ exome

AF:

0.0406

Gnomad EAS exome

AF:

0.0264

Gnomad SAS exome

AF:

0.0322

Gnomad FIN exome

AF:

0.00625

Gnomad NFE exome

AF:

0.0113

Gnomad OTH exome

AF:

0.0164

GnomAD4 exome

AF:

0.0114

AC:

16533

AN:

1447484

Hom.:

172

Cov.:

AF XY:

0.0124

AC XY:

8918

AN XY:

720902

show subpopulations

Gnomad4 AFR exome

AF:

0.00242

Gnomad4 AMR exome

AF:

0.00828

Gnomad4 ASJ exome

AF:

0.0395

Gnomad4 EAS exome

AF:

0.0161

Gnomad4 SAS exome

AF:

0.0326

Gnomad4 FIN exome

AF:

0.00651

Gnomad4 NFE exome

AF:

0.00937

Gnomad4 OTH exome

AF:

0.0130

GnomAD4 genome

AF:

0.00980

AC:

1491

AN:

152204

Hom.:

Cov.:

AF XY:

0.00970

AC XY:

722

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00234

Gnomad4 AMR

AF:

0.0132

Gnomad4 ASJ

AF:

0.0372

Gnomad4 EAS

AF:

0.0189

Gnomad4 SAS

AF:

0.0249

Gnomad4 FIN

AF:

0.00689

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.00984

Hom.:

Bravo

AF:

0.0108

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 06, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.93

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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