rs12681567

Variant names:

• chr8-15800094-C-A
• rs12681567
• NM_001413679.1:c.938-6269C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-15800094-C-A
• chr8-15800094-C-T

Variant summary

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

The NM_001413679.1(TUSC3):​c.938-6269C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0998 in 152,216 control chromosomes in the GnomAD database, including 1,099 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 0.10 (1099 hom., cov: 32)
• Consequence: TUSC3 NM_001413679.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• Publications: 2 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: Labcorp Genetics (formerly Invitae), G2P
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001413679.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUSC3	NM_001413679.1		c.938-6269C>A		intron	N/A	NP_001400608.1
	TUSC3	NM_001413684.1		c.1029-6269C>A		intron	N/A	NP_001400613.1
	TUSC3	NM_001413685.1		c.938-51430C>A		intron	N/A	NP_001400614.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.0998 AC: 15176 AN: 152098 Hom.: 1090 Cov.: 32

Gnomad AFR AF: 0.0310

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0599

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.0998 AC: 15197 AN: 152216 Hom.: 1099 Cov.: 32 AF XY: 0.103 AC XY: 7688 AN XY: 74416

African (AFR) AF: 0.0309 AC: 1284 AN: 41564

American (AMR) AF: 0.211 AC: 3222 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 497 AN: 3470

East Asian (EAS) AF: 0.255 AC: 1317 AN: 5168

South Asian (SAS) AF: 0.147 AC: 706 AN: 4818

European-Finnish (FIN) AF: 0.0599 AC: 635 AN: 10596

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.104 AC: 7064 AN: 68006

Other (OTH) AF: 0.117 AC: 248 AN: 2114

Alfa AF: 0.113 Hom.: 1306

Bravo AF: 0.108

Asia WGS AF: 0.204 AC: 706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.26
DANN	Benign	0.77
PhyloP100		-0.071

Splicing

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

Other links and lift over

dbSNP: rs12681567; hg19: chr8-15657603;