11-65967703-G-C

Variant names:

• chr11-65967703-G-C
• rs660118
• NM_005146.5:c.1454G>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.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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (12016 hom., cov: 31)
  • Exomes 𝑓: 0.45 (149052 hom.)
• Consequence: SART1 NM_005146.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 35 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 (MetaRNN=3.7430214E-5).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.53 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SART1	NM_005146.5	MANE Select	c.1454G>C	p.Gly485Ala	missense	Exon 12 of 20	NP_005137.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SART1	ENST00000312397.10	TSL:1 MANE Select	c.1454G>C	p.Gly485Ala	missense	Exon 12 of 20	ENSP00000310448.5

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

GnomAD2 exomes AF: 0.458 AC: 78175 AN: 170626 AF XY: 0.454

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 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

African (AFR) AF: 0.0879 AC: 2871 AN: 32668

American (AMR) AF: 0.639 AC: 23007 AN: 35992

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 11970 AN: 25182

East Asian (EAS) AF: 0.563 AC: 21084 AN: 37436

South Asian (SAS) AF: 0.426 AC: 34274 AN: 80396

European-Finnish (FIN) AF: 0.400 AC: 19723 AN: 49336

Middle Eastern (MID) AF: 0.356 AC: 1890 AN: 5308

European-Non Finnish (NFE) AF: 0.460 AC: 498799 AN: 1084238

Other (OTH) AF: 0.445 AC: 26005 AN: 58406

GnomAD4 genome AF: 0.363 AC: 55180 AN: 152016 Hom.: 12016 Cov.: 31 AF XY: 0.365 AC XY: 27148 AN XY: 74298

African (AFR) AF: 0.108 AC: 4488 AN: 41504

American (AMR) AF: 0.540 AC: 8247 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1669 AN: 3468

East Asian (EAS) AF: 0.520 AC: 2666 AN: 5124

South Asian (SAS) AF: 0.433 AC: 2085 AN: 4820

European-Finnish (FIN) AF: 0.391 AC: 4139 AN: 10582

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30500 AN: 67916

Other (OTH) AF: 0.384 AC: 811 AN: 2112

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 v4.9

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
PhyloP100		1.7
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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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