rs754532

Variant names:

• chr11-65979586-G-A
• rs754532
• NM_005146.5:c.*556G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.301 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SART1	NM_005146.5	MANE Select	c.*556G>A		3_prime_UTR	Exon 20 of 20	NP_005137.1	O43290-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SART1	ENST00000312397.10	TSL:1 MANE Select	c.*556G>A		3_prime_UTR	Exon 20 of 20	ENSP00000310448.5	O43290-1

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

African (AFR) AF: 0.154 AC: 8 AN: 52

American (AMR) AF: 0.189 AC: 71 AN: 376

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 9 AN: 48

East Asian (EAS) AF: 0.167 AC: 19 AN: 114

South Asian (SAS) AF: 0.377 AC: 89 AN: 236

European-Finnish (FIN) AF: 0.346 AC: 18 AN: 52

Middle Eastern (MID) AF: 0.750 AC: 3 AN: 4

European-Non Finnish (NFE) AF: 0.298 AC: 729 AN: 2448

Other (OTH) AF: 0.228 AC: 42 AN: 184

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

African (AFR) AF: 0.157 AC: 6515 AN: 41456

American (AMR) AF: 0.222 AC: 3385 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 854 AN: 3470

East Asian (EAS) AF: 0.160 AC: 826 AN: 5158

South Asian (SAS) AF: 0.314 AC: 1511 AN: 4814

European-Finnish (FIN) AF: 0.409 AC: 4307 AN: 10542

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20647 AN: 67942

Other (OTH) AF: 0.250 AC: 528 AN: 2114

Alfa AF: 0.277 Hom.: 13208

Bravo AF: 0.233

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	0.41
PhyloP100		-1.3
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: rs754532; hg19: chr11-65747057;