NM_001413679.1:c.938-18832A>T

Variant names:

• chr8-15787531-A-T
• rs352769
• NM_001413679.1:c.938-18832A>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.938-18832A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 152,280 control chromosomes in the GnomAD database, including 142 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 0.039 (142 hom., cov: 32)
• Consequence: TUSC3 NM_001413679.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• Publications: 4 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUSC3	NM_001413679.1	c.938-18832A>T		intron_variant	Intron 8 of 8		NP_001400608.1
TUSC3	NM_001413684.1	c.1029-18832A>T		intron_variant	Intron 9 of 9		NP_001400613.1
TUSC3	NM_001413685.1	c.937+43919A>T		intron_variant	Intron 8 of 8		NP_001400614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0391 AC: 5945 AN: 152162 Hom.: 141 Cov.: 32

Gnomad AFR AF: 0.0721

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0290

Gnomad ASJ AF: 0.0625

Gnomad EAS AF: 0.0371

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0253

Gnomad OTH AF: 0.0439

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

GnomAD4 genome AF: 0.0392 AC: 5963 AN: 152280 Hom.: 142 Cov.: 32 AF XY: 0.0389 AC XY: 2896 AN XY: 74462

African (AFR) AF: 0.0723 AC: 3001 AN: 41536

American (AMR) AF: 0.0290 AC: 443 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0625 AC: 217 AN: 3472

East Asian (EAS) AF: 0.0370 AC: 192 AN: 5186

South Asian (SAS) AF: 0.0294 AC: 142 AN: 4828

European-Finnish (FIN) AF: 0.0132 AC: 140 AN: 10626

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0253 AC: 1722 AN: 68012

Other (OTH) AF: 0.0435 AC: 92 AN: 2116

Alfa AF: 0.00465 Hom.: 0

Bravo AF: 0.0415

Asia WGS AF: 0.0410 AC: 143 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.0090
DANN	Benign	0.80
PhyloP100		-2.3

Splicing

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

Other links and lift over

dbSNP: rs352769; hg19: chr8-15645040;