rs7837736

chr8-15439194-G-A

Variant summary

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

The XR_007061172.1(LOC124902059):n.257+5598C>T variant causes a intron, non coding transcript 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: LOC124902059 XR_007061172.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

Genes affected

LOC124902059 (HGNC:):

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124902059	XR_007061172.1	n.257+5598C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUSC3	ENST00000503191.5	n.91+21889G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.0211

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.184

Alfa AF: 0.158 Hom.: 319

Bravo AF: 0.162

Asia WGS AF: 0.0850 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.020
Dann	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7837736; hg19: chr8-15296703;