rs587780496

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_006765.4(TUSC3):c.1028+8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000414 in 1,569,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

TUSC3
NM_006765.4 splice_region, intron

Scores

Splicing: ADA: 0.00002697

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.189

Publications

0 publications found

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 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

TUSC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 8-15748473-C-G is Benign according to our data. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-15748473-C-G is described in CliVar as Likely_benign. Clinvar id is 130691.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUSC3	NM_006765.4 link	c.1028+8C>G		splice_region_variant, intron_variant	Intron 9 of 10	ENST00000503731.6	NP_006756.2	Q13454-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUSC3	ENST00000503731.6 link	c.1028+8C>G		splice_region_variant, intron_variant	Intron 9 of 10	1	NM_006765.4	ENSP00000424544.1		Q13454-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

251028

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000437

AC:

AN:

1417158

Hom.:

Cov.:

AF XY:

0.0000395

AC XY:

AN XY:

708022

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32536

American (AMR)

AF:

0.00

AC:

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25882

East Asian (EAS)

AF:

0.00

AC:

AN:

39376

South Asian (SAS)

AF:

0.00

AC:

AN:

85306

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53150

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

0.0000532

AC:

AN:

1071622

Other (OTH)

AF:

0.0000848

AC:

AN:

58962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152010

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41412

American (AMR)

AF:

0.00

AC:

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67944

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 17, 2014

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

TUSC3-related disorder

Benign:1

Feb 28, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

2.1

(source)

DANN

Benign

0.60

PhyloP100

-0.19

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000027

dbscSNV1_RF

Benign

0.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over