rs4831732

Positions:

• chr8-15511976-C-A
• chr8-15511976-C-G
• chr8-15511976-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001413670.1(TUSC3):​c.78+89056C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.953 in 152,200 control chromosomes in the GnomAD database, including 69,470 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.95 (69470 hom., cov: 32)
• Consequence: TUSC3 NM_001413670.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUSC3	NM_001413669.1	c.-31+94671C>A		intron_variant
TUSC3	NM_001413670.1	c.78+89056C>A		intron_variant
TUSC3	NM_001413671.1	c.-31+94671C>A		intron_variant
TUSC3	NM_001413672.1	c.-31+28493C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUSC3	ENST00000503191.5	n.189+28493C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.953 AC: 144896 AN: 152082 Hom.: 69418 Cov.: 32

Gnomad AFR AF: 0.839

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.978

Gnomad ASJ AF: 0.996

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.964

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.953 AC: 145009 AN: 152200 Hom.: 69470 Cov.: 32 AF XY: 0.954 AC XY: 71029 AN XY: 74428

Gnomad4 AFR AF: 0.839

Gnomad4 AMR AF: 0.978

Gnomad4 ASJ AF: 0.996

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.964

Alfa AF: 0.984 Hom.: 3484

Bravo AF: 0.946

Asia WGS AF: 0.991 AC: 3447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.75
DANN	Benign	0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4831732; hg19: chr8-15369485;