rs1908465

Variant names:

• chr8-15450924-T-A
• rs1908465
• NM_001413670.1:c.78+28004T>A

Your query was ambiguous. Multiple possible variants found:

• chr8-15450924-T-A
• chr8-15450924-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001413670.1(TUSC3):​c.78+28004T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 151,984 control chromosomes in the GnomAD database, including 39,690 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 0.72 (39690 hom., cov: 31)
• Consequence: TUSC3 NM_001413670.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUSC3	NM_001413670.1	c.78+28004T>A		intron_variant	Intron 2 of 10		NP_001400599.1
TUSC3	NM_001413671.1	c.-31+33619T>A		intron_variant	Intron 1 of 10		NP_001400600.1
TUSC3	NM_001413669.1	c.-31+33619T>A		intron_variant	Intron 1 of 9		NP_001400598.1
TUSC3	NM_001413672.1	c.-128-32462T>A		intron_variant	Intron 1 of 10		NP_001400601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUSC3	ENST00000503191.5	n.92-32462T>A		intron_variant	Intron 1 of 5	3

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109509 AN: 151870 Hom.: 39661 Cov.: 31

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.721 AC: 109589 AN: 151984 Hom.: 39690 Cov.: 31 AF XY: 0.725 AC XY: 53877 AN XY: 74280

African (AFR) AF: 0.698 AC: 28965 AN: 41468

American (AMR) AF: 0.757 AC: 11560 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2269 AN: 3468

East Asian (EAS) AF: 0.886 AC: 4535 AN: 5118

South Asian (SAS) AF: 0.685 AC: 3300 AN: 4818

European-Finnish (FIN) AF: 0.765 AC: 8083 AN: 10572

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.717 AC: 48699 AN: 67952

Other (OTH) AF: 0.719 AC: 1519 AN: 2114

Alfa AF: 0.721 Hom.: 4702

Bravo AF: 0.719

Asia WGS AF: 0.797 AC: 2770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.0
DANN	Benign	0.79
PhyloP100		0.20

Splicing

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

Other links and lift over

dbSNP: rs1908465; hg19: chr8-15308433;