11-65965763-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005146.5(SART1):​c.722T>C​(p.Phe241Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SART1
NM_005146.5 missense

Scores

1
8
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.75
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SART1NM_005146.5 linkuse as main transcriptc.722T>C p.Phe241Ser missense_variant 6/20 ENST00000312397.10
SART1XM_047427856.1 linkuse as main transcriptc.722T>C p.Phe241Ser missense_variant 6/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SART1ENST00000312397.10 linkuse as main transcriptc.722T>C p.Phe241Ser missense_variant 6/201 NM_005146.5 P1O43290-1
SART1ENST00000529532.5 linkuse as main transcriptn.816T>C non_coding_transcript_exon_variant 6/92

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.62
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.027
T
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.86
D
M_CAP
Benign
0.021
T
MetaRNN
Uncertain
0.55
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.19
Sift
Benign
0.28
T
Sift4G
Uncertain
0.034
D
Polyphen
0.98
D
Vest4
0.58
MutPred
0.47
Gain of relative solvent accessibility (P = 0.0023);
MVP
0.36
MPC
1.3
ClinPred
0.85
D
GERP RS
4.2
Varity_R
0.13
gMVP
0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65733234; API