rs754532

Positions:

• chr11-65979586-G-A
• chr11-65979586-G-C

Variant summary

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

The NM_005146.5(SART1):​c.*556G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 155,480 control chromosomes in the GnomAD database, including 5,559 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 0.26 (5421 hom., cov: 31)
  • Exomes 𝑓: 0.28 (138 hom.)
• Consequence: SART1 NM_005146.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SART1	NM_005146.5	c.*556G>A		3_prime_UTR_variant	20/20	ENST00000312397.10	NP_005137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SART1	ENST00000312397.10	c.*556G>A		3_prime_UTR_variant	20/20	1	NM_005146.5	ENSP00000310448	P1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38816 AN: 151848 Hom.: 5419 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.281 AC: 988 AN: 3514 Hom.: 138 Cov.: 0 AF XY: 0.282 AC XY: 504 AN XY: 1790

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.377

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.255 AC: 38826 AN: 151966 Hom.: 5421 Cov.: 31 AF XY: 0.261 AC XY: 19385 AN XY: 74278

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.250

Alfa AF: 0.282 Hom.: 8970

Bravo AF: 0.233

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	0.41

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: rs754532; hg19: chr11-65747057;