Genetic Variant SART1:p.Arg164Pro (chr11-65965155-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_005146.5(SART1):c.491G>C(p.Arg164Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000936 in 1,603,374 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

SART1
NM_005146.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05

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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SART1	NM_005146.5 link	c.491G>C	p.Arg164Pro	missense_variant	Exon 4 of 20	ENST00000312397.10	NP_005137.1	O43290-1
SART1	XM_047427856.1 link	c.491G>C	p.Arg164Pro	missense_variant	Exon 4 of 13		XP_047283812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SART1	ENST00000312397.10 link	c.491G>C	p.Arg164Pro	missense_variant	Exon 4 of 20	1	NM_005146.5	ENSP00000310448.5		O43290-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000125

AC:

AN:

239552

AF XY:

0.00000764

show subpopulations

Gnomad AFR exome

AF:

0.0000636

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000758

AC:

AN:

1451162

Hom.:

Cov.:

AF XY:

0.00000554

AC XY:

AN XY:

722548

show subpopulations

Gnomad4 AFR exome

AF:

0.0000616

AC:

AN:

32480

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

40196

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25718

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39664

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

85402

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

52618

Gnomad4 NFE exome

AF:

0.00000811

AC:

AN:

1109540

Gnomad4 Remaining exome

AF:

0.00

AC:

AN:

59922

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<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:

0.0000263

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000241

AC:

0.0000241231

AN:

0.0000241231

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000441

AC:

0.0000440878

AN:

0.0000440878

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<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:

0.0000282

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 02, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.491G>C (p.R164P) alteration is located in exon 4 (coding exon 4) of the SART1 gene. This alteration results from a G to C substitution at nucleotide position 491, causing the arginine (R) at amino acid position 164 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.057

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.8

REVEL

Benign

0.22

Sift

Benign

0.18

Sift4G

Benign

0.25

Polyphen

0.99

Vest4

0.52

MVP

0.53

MPC

0.76

ClinPred

0.53

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.67

gMVP

0.68

Mutation Taster

=84/16

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over