11-65967703-G-C

Position:

• chr11-65967703-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000312397.10(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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.36 (12016 hom., cov: 31)
  • Exomes 𝑓: 0.45 (149052 hom.)
• Consequence: SART1 ENST00000312397.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72

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

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/exons	MANE	Protein	UniProt
SART1	NM_005146.5	c.1454G>C	p.Gly485Ala	missense_variant	12/20	ENST00000312397.10	NP_005137.1
SART1	XM_047427856.1	c.1454G>C	p.Gly485Ala	missense_variant	12/13		XP_047283812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SART1	ENST00000312397.10	c.1454G>C	p.Gly485Ala	missense_variant	12/20	1	NM_005146.5	ENSP00000310448	P1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55164 AN: 151898 Hom.: 12009 Cov.: 31

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

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.: 54 AF XY: 0.453 AC XY: 314721 AN XY: 695332

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.: 31 AF XY: 0.365 AC XY: 27148 AN XY: 74298

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	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.67
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.000037	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.0055	P
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.054
Sift	Benign	0.44	T
Sift4G	Benign	0.90	T
Polyphen		0.27	B
Vest4		0.16
MPC		0.31
ClinPred		0.0028	T
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

Other links and lift over

dbSNP: rs660118; hg19: chr11-65735174; COSMIC: COSV56710544; COSMIC: COSV56710544;