11-65976832-C-T

Variant names:

• chr11-65976832-C-T
• rs2276015
• NM_005146.5:c.1857+66C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005146.5(SART1):​c.1857+66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00704 in 1,381,676 control chromosomes in the GnomAD database, including 562 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 0.014 (79 hom., cov: 33)
  • Exomes 𝑓: 0.0061 (483 hom.)
• Consequence: SART1 NM_005146.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 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.1857+66C>T		intron	N/A	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.1857+66C>T		intron	N/A	ENSP00000310448.5	O43290-1
	SART1	ENST00000972145.1		c.1869+66C>T		intron	N/A	ENSP00000642204.1
	SART1	ENST00000972146.1		c.1851+66C>T		intron	N/A	ENSP00000642205.1

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2174 AN: 152150 Hom.: 78 Cov.: 33

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.00766

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.00613 AC: 7542 AN: 1229408 Hom.: 483 Cov.: 17 AF XY: 0.00595 AC XY: 3646 AN XY: 612606

African (AFR) AF: 0.0269 AC: 769 AN: 28626

American (AMR) AF: 0.0112 AC: 394 AN: 35096

Ashkenazi Jewish (ASJ) AF: 0.00195 AC: 44 AN: 22548

East Asian (EAS) AF: 0.153 AC: 5396 AN: 35312

South Asian (SAS) AF: 0.00400 AC: 296 AN: 73974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47740

Middle Eastern (MID) AF: 0.00174 AC: 7 AN: 4032

European-Non Finnish (NFE) AF: 0.000103 AC: 96 AN: 929954

Other (OTH) AF: 0.0104 AC: 540 AN: 52126

GnomAD4 genome AF: 0.0143 AC: 2185 AN: 152268 Hom.: 79 Cov.: 33 AF XY: 0.0159 AC XY: 1185 AN XY: 74448

African (AFR) AF: 0.0251 AC: 1043 AN: 41546

American (AMR) AF: 0.0165 AC: 252 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.155 AC: 802 AN: 5170

South Asian (SAS) AF: 0.00808 AC: 39 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68016

Other (OTH) AF: 0.0123 AC: 26 AN: 2114

Alfa AF: 0.00386 Hom.: 7

Bravo AF: 0.0168

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.3
DANN	Benign	0.68
PhyloP100		0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2276015;

hg19: chr11-65744303;

COSMIC: COSV56714024;

COSMIC: COSV56714024;