8-15540340-G-A

Position:

chr8-15540340-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000503731(TUSC3):c.-91G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,375,936 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.010 ( 22 hom., cov: 32)

Exomes 𝑓: 0.00093 ( 23 hom. )

Consequence

TUSC3
ENST00000503731 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0470

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 8-15540340-G-A is Benign according to our data. Variant chr8-15540340-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 910998.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0103 (1570/152282) while in subpopulation AFR AF= 0.0348 (1446/41570). AF 95% confidence interval is 0.0333. There are 22 homozygotes in gnomad4. There are 772 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUSC3	NM_006765.4 linkuse as main transcript	c.-91G>A		5_prime_UTR_variant	1/11	ENST00000503731.6	NP_006756.2	Q13454-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUSC3	ENST00000503731 linkuse as main transcript	c.-91G>A		5_prime_UTR_variant	1/11	1	NM_006765.4	ENSP00000424544.1		Q13454-1

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1564

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0347

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00556

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00813

GnomAD4 exome

AF:

0.000925

AC:

1132

AN:

1223654

Hom.:

Cov.:

AF XY:

0.000765

AC XY:

453

AN XY:

592532

show subpopulations

Gnomad4 AFR exome

AF:

0.0365

Gnomad4 AMR exome

AF:

0.00436

Gnomad4 ASJ exome

AF:

0.00229

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000271

Gnomad4 OTH exome

AF:

0.00255

GnomAD4 genome

AF:

0.0103

AC:

1570

AN:

152282

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

772

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0348

Gnomad4 AMR

AF:

0.00555

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00673

Hom.:

Bravo

AF:

0.0118

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital disorder of glycosylation

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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