rs573872013

Variant names:

• chr8-15540241-C-A
• rs573872013
• ENST00000382020.8:c.-190C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-15540241-C-A
• chr8-15540241-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178234.2(TUSC3):​c.-190C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000152 in 657,092 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: TUSC3 NM_178234.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178234.2. 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_178234.2		c.-190C>A		5_prime_UTR	Exon 1 of 10	NP_839952.1	Q13454-2
	TUSC3	NM_001413670.1		c.79-82839C>A		intron	N/A	NP_001400599.1
	TUSC3	NM_001413671.1		c.-30-82839C>A		intron	N/A	NP_001400600.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUSC3	ENST00000382020.8	TSL:1	c.-190C>A		5_prime_UTR	Exon 1 of 10	ENSP00000371450.4	Q13454-2
	TUSC3	ENST00000877722.1		c.-190C>A		5_prime_UTR	Exon 1 of 11	ENSP00000547781.1
	TUSC3	ENST00000928815.1		c.-190C>A		5_prime_UTR	Exon 1 of 10	ENSP00000598874.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000152 AC: 1 AN: 657092 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 326266

African (AFR) AF: 0.0000743 AC: 1 AN: 13454

American (AMR) AF: 0.00 AC: 0 AN: 7958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12398

East Asian (EAS) AF: 0.00 AC: 0 AN: 24164

South Asian (SAS) AF: 0.00 AC: 0 AN: 29608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2200

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 509736

Other (OTH) AF: 0.00 AC: 0 AN: 30684

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	16
DANN	Benign	0.95
PhyloP100		1.1
PromoterAI		-0.19	Neutral

Splicing

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

Other links and lift over

dbSNP: rs573872013; hg19: chr8-15397750;