rs10081561

Variant names:

• chr8-15639822-G-A
• rs10081561
• NM_006765.4:c.309-10875G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-15639822-G-A
• chr8-15639822-G-C
• chr8-15639822-G-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.309-10875G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 145,982 control chromosomes in the GnomAD database, including 22,103 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 0.55 (22103 hom., cov: 26)
• Consequence: TUSC3 NM_001413679.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• 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: 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUSC3	NM_006765.4	MANE Select	c.309-10875G>A		intron	N/A	NP_006756.2
	TUSC3	NM_001413679.1		c.309-10875G>A		intron	N/A	NP_001400608.1
	TUSC3	NM_001413684.1		c.309-10875G>A		intron	N/A	NP_001400613.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUSC3	ENST00000503731.6	TSL:1 MANE Select	c.309-10875G>A		intron	N/A	ENSP00000424544.1
	TUSC3	ENST00000382020.8	TSL:1	c.309-10875G>A		intron	N/A	ENSP00000371450.4
	TUSC3	ENST00000947282.1		c.384-10875G>A		intron	N/A	ENSP00000617341.1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 80491 AN: 145914 Hom.: 22084 Cov.: 26

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.552 AC: 80537 AN: 145982 Hom.: 22103 Cov.: 26 AF XY: 0.554 AC XY: 39231 AN XY: 70838

African (AFR) AF: 0.462 AC: 18304 AN: 39596

American (AMR) AF: 0.557 AC: 8164 AN: 14656

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1908 AN: 3412

East Asian (EAS) AF: 0.634 AC: 3037 AN: 4788

South Asian (SAS) AF: 0.511 AC: 2264 AN: 4430

European-Finnish (FIN) AF: 0.668 AC: 6076 AN: 9098

Middle Eastern (MID) AF: 0.565 AC: 157 AN: 278

European-Non Finnish (NFE) AF: 0.584 AC: 39029 AN: 66794

Other (OTH) AF: 0.537 AC: 1095 AN: 2038

Alfa AF: 0.559 Hom.: 36409

Bravo AF: 0.535

Asia WGS AF: 0.560 AC: 1942 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.11
DANN	Benign	0.40
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10081561; hg19: chr8-15497331;