rs679581

Positions:

• chr11-65979182-A-G

Variant summary

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

The NM_005146.5(SART1):​c.*152A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 926,216 control chromosomes in the GnomAD database, including 96,530 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 0.40 (12928 hom., cov: 32)
  • Exomes 𝑓: 0.46 (83602 hom.)
• Consequence: SART1 NM_005146.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

Genes affected

SART1 (HGNC:10538): (spliceosome associated factor 1, recruiter of U4/U6.U5 tri-snRNP) This gene encodes two proteins, the SART1(800) protein expressed in the nucleus of the majority of proliferating cells, and the SART1(259) protein expressed in the cytosol of epithelial cancers. The SART1(259) protein is translated by the mechanism of -1 frameshifting during posttranscriptional regulation; its full-length sequence is not published yet. The two encoded proteins are thought to be involved in the regulation of proliferation. Both proteins have tumor-rejection antigens. The SART1(259) protein possesses tumor epitopes capable of inducing HLA-A2402-restricted cytotoxic T lymphocytes in cancer patients. This SART1(259) antigen may be useful in specific immunotherapy for cancer patients and may serve as a paradigmatic tool for the diagnosis and treatment of patients with atopy. The SART1(259) protein is found to be essential for the recruitment of the tri-snRNP to the pre-spliceosome in the spliceosome assembly pathway. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SART1	NM_005146.5	c.*152A>G		3_prime_UTR_variant	20/20	ENST00000312397.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SART1	ENST00000312397.10	c.*152A>G		3_prime_UTR_variant	20/20	1	NM_005146.5	P1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60148 AN: 151934 Hom.: 12919 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.459 AC: 355026 AN: 774164 Hom.: 83602 Cov.: 10 AF XY: 0.457 AC XY: 180564 AN XY: 395502

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.628

Gnomad4 ASJ exome AF: 0.478

Gnomad4 EAS exome AF: 0.569

Gnomad4 SAS exome AF: 0.442

Gnomad4 FIN exome AF: 0.388

Gnomad4 NFE exome AF: 0.460

Gnomad4 OTH exome AF: 0.454

GnomAD4 genome AF: 0.396 AC: 60174 AN: 152052 Hom.: 12928 Cov.: 32 AF XY: 0.397 AC XY: 29530 AN XY: 74346

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.407

Alfa AF: 0.450 Hom.: 26495

Bravo AF: 0.404

Asia WGS AF: 0.501 AC: 1741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs679581; hg19: chr11-65746653;