Genetic Variant SART1:c.1857+66C>T (chr11-65976832-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.223

Publications

2 publications found

Variant links:

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]

SART1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SART1	NM_005146.5 link	c.1857+66C>T		intron_variant	Intron 14 of 19	ENST00000312397.10	NP_005137.1	O43290-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SART1	ENST00000312397.10 link	c.1857+66C>T		intron_variant	Intron 14 of 19	1	NM_005146.5	ENSP00000310448.5		O43290-1
SART1	ENST00000533386.1 link	n.18+66C>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2174

AN:

152150

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00595

AC XY:

3646

AN XY:

612606

show subpopulations

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:

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:

AN:

47740

Middle Eastern (MID)

AF:

0.00174

AC:

AN:

4032

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

929954

Other (OTH)

AF:

0.0104

AC:

540

AN:

52126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

402

805

1207

1610

2012

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

220

330

440

550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0143

AC:

2185

AN:

152268

Hom.:

Cov.:

AF XY:

0.0159

AC XY:

1185

AN XY:

74448

show subpopulations

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:

AN:

3470

East Asian (EAS)

AF:

0.155

AC:

802

AN:

5170

South Asian (SAS)

AF:

0.00808

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68016

Other (OTH)

AF:

0.0123

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

105

209

314

418

523

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00386

Hom.:

Bravo

AF:

0.0168

Asia WGS

AF:

0.0520

AC:

180

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.3

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over