chr11-65979182-A-G

Variant names:

• chr11-65979182-A-G
• rs679581
• NM_005146.5:c.*152A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005146.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SART1	NM_005146.5	MANE Select	c.*152A>G		3_prime_UTR	Exon 20 of 20	NP_005137.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SART1	ENST00000312397.10	TSL:1 MANE Select	c.*152A>G		3_prime_UTR	Exon 20 of 20	ENSP00000310448.5
	SART1	ENST00000528137.1	TSL:2	n.*93A>G		downstream_gene	N/A
	SART1	ENST00000529580.1	TSL:2	n.*225A>G		downstream_gene	N/A

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

African (AFR) AF: 0.219 AC: 4153 AN: 18944

American (AMR) AF: 0.628 AC: 17223 AN: 27406

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 8323 AN: 17404

East Asian (EAS) AF: 0.569 AC: 18627 AN: 32756

South Asian (SAS) AF: 0.442 AC: 25728 AN: 58232

European-Finnish (FIN) AF: 0.388 AC: 17721 AN: 45640

Middle Eastern (MID) AF: 0.348 AC: 1432 AN: 4112

European-Non Finnish (NFE) AF: 0.460 AC: 245132 AN: 532884

Other (OTH) AF: 0.454 AC: 16687 AN: 36786

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

African (AFR) AF: 0.223 AC: 9268 AN: 41472

American (AMR) AF: 0.549 AC: 8382 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1689 AN: 3468

East Asian (EAS) AF: 0.524 AC: 2706 AN: 5168

South Asian (SAS) AF: 0.453 AC: 2183 AN: 4820

European-Finnish (FIN) AF: 0.379 AC: 4015 AN: 10584

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30497 AN: 67950

Other (OTH) AF: 0.407 AC: 859 AN: 2108

Alfa AF: 0.440 Hom.: 59092

Bravo AF: 0.404

Asia WGS AF: 0.501 AC: 1741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.44
PhyloP100		0.040
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: rs679581; hg19: chr11-65746653;