NM_006765.4:c.139-30294G>C

Variant names:

• chr8-15592786-G-C
• rs1579451
• NM_006765.4:c.139-30294G>C

Variant summary

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

The NM_006765.4(TUSC3):​c.139-30294G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 151,974 control chromosomes in the GnomAD database, including 23,567 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 (23567 hom., cov: 32)
• Consequence: TUSC3 NM_006765.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 1 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006765.4. 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_006765.4	MANE Select	c.139-30294G>C		intron	N/A	NP_006756.2
	TUSC3	NM_001413679.1		c.139-30294G>C		intron	N/A	NP_001400608.1
	TUSC3	NM_001413684.1		c.139-30294G>C		intron	N/A	NP_001400613.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUSC3	ENST00000503731.6	TSL:1 MANE Select	c.139-30294G>C		intron	N/A	ENSP00000424544.1	Q13454-1
	TUSC3	ENST00000382020.8	TSL:1	c.139-30294G>C		intron	N/A	ENSP00000371450.4	Q13454-2
	TUSC3	ENST00000947282.1		c.214-30294G>C		intron	N/A	ENSP00000617341.1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84158 AN: 151854 Hom.: 23539 Cov.: 32

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.554 AC: 84222 AN: 151974 Hom.: 23567 Cov.: 32 AF XY: 0.556 AC XY: 41283 AN XY: 74272

African (AFR) AF: 0.606 AC: 25116 AN: 41436

American (AMR) AF: 0.474 AC: 7243 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1888 AN: 3470

East Asian (EAS) AF: 0.630 AC: 3245 AN: 5152

South Asian (SAS) AF: 0.510 AC: 2448 AN: 4804

European-Finnish (FIN) AF: 0.596 AC: 6284 AN: 10550

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36132 AN: 67970

Other (OTH) AF: 0.551 AC: 1164 AN: 2112

Alfa AF: 0.379 Hom.: 942

Bravo AF: 0.549

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.54
PhyloP100		-1.4
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: rs1579451; hg19: chr8-15450295;