Genetic Variant SART1:p.Gly485Ala (chr11-65967703-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005146.5(SART1):c.1454G>C(p.Gly485Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,560,978 control chromosomes in the GnomAD database, including 161,068 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.36 ( 12016 hom., cov: 31)

Exomes 𝑓: 0.45 ( 149052 hom. )

Consequence

SART1
NM_005146.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.72

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.7430214E-5).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SART1	NM_005146.5 link	c.1454G>C	p.Gly485Ala	missense_variant	Exon 12 of 20	ENST00000312397.10	NP_005137.1	O43290-1
SART1	XM_047427856.1 link	c.1454G>C	p.Gly485Ala	missense_variant	Exon 12 of 13		XP_047283812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SART1	ENST00000312397.10 link	c.1454G>C	p.Gly485Ala	missense_variant	Exon 12 of 20	1	NM_005146.5	ENSP00000310448.5		O43290-1

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55164

AN:

151898

Hom.:

12009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.540

Gnomad ASJ

AF:

0.481

Gnomad EAS

AF:

0.519

Gnomad SAS

AF:

0.433

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.449

Gnomad OTH

AF:

0.381

GnomAD3 exomes

AF:

0.458

AC:

78175

AN:

170626

Hom.:

19181

AF XY:

0.454

AC XY:

41261

AN XY:

90818

show subpopulations

Gnomad AFR exome

AF:

0.0989

Gnomad AMR exome

AF:

0.654

Gnomad ASJ exome

AF:

0.482

Gnomad EAS exome

AF:

0.508

Gnomad SAS exome

AF:

0.427

Gnomad FIN exome

AF:

0.394

Gnomad NFE exome

AF:

0.451

Gnomad OTH exome

AF:

0.459

GnomAD4 exome

AF:

0.454

AC:

639623

AN:

1408962

Hom.:

149052

Cov.:

AF XY:

0.453

AC XY:

314721

AN XY:

695332

show subpopulations

Gnomad4 AFR exome

AF:

0.0879

Gnomad4 AMR exome

AF:

0.639

Gnomad4 ASJ exome

AF:

0.475

Gnomad4 EAS exome

AF:

0.563

Gnomad4 SAS exome

AF:

0.426

Gnomad4 FIN exome

AF:

0.400

Gnomad4 NFE exome

AF:

0.460

Gnomad4 OTH exome

AF:

0.445

GnomAD4 genome

AF:

0.363

AC:

55180

AN:

152016

Hom.:

12016

Cov.:

AF XY:

0.365

AC XY:

27148

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.108

Gnomad4 AMR

AF:

0.540

Gnomad4 ASJ

AF:

0.481

Gnomad4 EAS

AF:

0.520

Gnomad4 SAS

AF:

0.433

Gnomad4 FIN

AF:

0.391

Gnomad4 NFE

AF:

0.449

Gnomad4 OTH

AF:

0.384

Alfa

AF:

0.429

Hom.:

4901

Bravo

AF:

0.367

TwinsUK

AF:

0.460

AC:

1704

ALSPAC

AF:

0.463

AC:

1785

ESP6500AA

AF:

0.102

AC:

442

ESP6500EA

AF:

0.415

AC:

3506

ExAC

AF:

0.365

AC:

40004

Asia WGS

AF:

0.486

AC:

1687

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.010

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.57

MetaRNN

Benign

0.000037

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.090

REVEL

Benign

0.054

Sift

Benign

0.44

Sift4G

Benign

0.90

Polyphen

0.27

Vest4

0.16

MPC

0.31

ClinPred

0.0028

GERP RS

4.2

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Varity_R

0.022

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over