rs2604357

chr8-15743653-C-Gchr8-15743653-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.905

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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 GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUSC3	NM_006765.4	c.937+41C>G		intron_variant		ENST00000503731.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUSC3	ENST00000503731.6	c.937+41C>G		intron_variant		1	NM_006765.4	A1

Frequencies

GnomAD3 genomes AF: 0.00980 AC: 1490 AN: 152086 Hom.: 9 Cov.: 33

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.: 47 AF XY: 0.0164 AC XY: 2212 AN XY: 135034

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.: 27 AF XY: 0.0124 AC XY: 8918 AN XY: 720902

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.: 9 Cov.: 33 AF XY: 0.00970 AC XY: 722 AN XY: 74404

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.: 6

Bravo AF: 0.0108

Asia WGS AF: 0.0150 AC: 51 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs2604357; hg19: chr8-15601162;