rs12550009

Variant names:

• chr8-15540311-C-T
• rs12550009
• NM_006765.4:c.-120C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-15540311-C-T
• chr8-15540311-C-A
• chr8-15540311-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006765.4(TUSC3):​c.-120C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,323,854 control chromosomes in the GnomAD database, including 27,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3137 hom., cov: 32)
  • Exomes 𝑓: 0.20 (24627 hom.)
• Consequence: TUSC3 NM_006765.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.162
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 8-15540311-C-T is Benign according to our data. Variant chr8-15540311-C-T is described in ClinVar as Benign. ClinVar VariationId is 362304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 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.-120C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_006756.2
	TUSC3	NM_006765.4	MANE Select	c.-120C>T		5_prime_UTR	Exon 1 of 11	NP_006756.2
	TUSC3	NM_001413679.1		c.-120C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_001400608.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUSC3	ENST00000503731.6	TSL:1 MANE Select	c.-120C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000424544.1	Q13454-1
	TUSC3	ENST00000382020.8	TSL:1	c.-120C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000371450.4	Q13454-2
	TUSC3	ENST00000503731.6	TSL:1 MANE Select	c.-120C>T		5_prime_UTR	Exon 1 of 11	ENSP00000424544.1	Q13454-1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30942 AN: 152042 Hom.: 3137 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.203 AC: 237953 AN: 1171696 Hom.: 24627 Cov.: 20 AF XY: 0.205 AC XY: 116100 AN XY: 566884

African (AFR) AF: 0.197 AC: 4492 AN: 22796

American (AMR) AF: 0.222 AC: 2308 AN: 10378

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 3881 AN: 16204

East Asian (EAS) AF: 0.268 AC: 7362 AN: 27426

South Asian (SAS) AF: 0.267 AC: 13425 AN: 50302

European-Finnish (FIN) AF: 0.200 AC: 6432 AN: 32126

Middle Eastern (MID) AF: 0.244 AC: 795 AN: 3254

European-Non Finnish (NFE) AF: 0.197 AC: 189624 AN: 960956

Other (OTH) AF: 0.200 AC: 9634 AN: 48254

GnomAD4 genome AF: 0.203 AC: 30951 AN: 152158 Hom.: 3137 Cov.: 32 AF XY: 0.205 AC XY: 15222 AN XY: 74394

African (AFR) AF: 0.196 AC: 8161 AN: 41558

American (AMR) AF: 0.205 AC: 3135 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 815 AN: 3470

East Asian (EAS) AF: 0.237 AC: 1212 AN: 5124

South Asian (SAS) AF: 0.265 AC: 1278 AN: 4826

European-Finnish (FIN) AF: 0.196 AC: 2075 AN: 10608

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13569 AN: 67962

Other (OTH) AF: 0.200 AC: 421 AN: 2110

Alfa AF: 0.103 Hom.: 148

Bravo AF: 0.206

Asia WGS AF: 0.219 AC: 760 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.90
PhyloP100		-0.16
PromoterAI		0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=300/0	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: rs12550009; hg19: chr8-15397820; COSMIC: COSV65881220;