8-15439194-G-A

Variant names:

• chr8-15439194-G-A
• rs7837736
• NM_001413670.1:c.78+16274G>A

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+16274G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,160 control chromosomes in the GnomAD database, including 2,083 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 0.16 (2083 hom., cov: 33)
• Consequence: TUSC3 NM_001413670.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42
• Publications: 6 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

LOC124902059 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001413670.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUSC3	NM_001413670.1		c.78+16274G>A		intron	N/A	NP_001400599.1
	TUSC3	NM_001413671.1		c.-31+21889G>A		intron	N/A	NP_001400600.1
	TUSC3	NM_001413669.1		c.-31+21889G>A		intron	N/A	NP_001400598.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUSC3	ENST00000503191.5	TSL:3	n.91+21889G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24704 AN: 152042 Hom.: 2081 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.162 AC: 24720 AN: 152160 Hom.: 2083 Cov.: 33 AF XY: 0.161 AC XY: 11957 AN XY: 74388

African (AFR) AF: 0.161 AC: 6672 AN: 41500

American (AMR) AF: 0.138 AC: 2107 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 782 AN: 3472

East Asian (EAS) AF: 0.0211 AC: 109 AN: 5178

South Asian (SAS) AF: 0.173 AC: 834 AN: 4820

European-Finnish (FIN) AF: 0.162 AC: 1714 AN: 10594

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.174 AC: 11815 AN: 67980

Other (OTH) AF: 0.184 AC: 390 AN: 2116

Alfa AF: 0.165 Hom.: 2877

Bravo AF: 0.162

Asia WGS AF: 0.0850 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.020
DANN	Benign	0.42
PhyloP100		-2.4

Splicing

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

Other links and lift over

dbSNP: rs7837736; hg19: chr8-15296703;