11-65965095-C-T

Position:

chr11-65965095-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000312397.10(SART1):c.431C>T(p.Ala144Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000604 in 1,573,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

SART1
ENST00000312397.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.16

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.050262988).

BS2

High AC in GnomAd4 at 36 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SART1	NM_005146.5 linkuse as main transcript	c.431C>T	p.Ala144Val	missense_variant	4/20	ENST00000312397.10	NP_005137.1
SART1	XM_047427856.1 linkuse as main transcript	c.431C>T	p.Ala144Val	missense_variant	4/13		XP_047283812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SART1	ENST00000312397.10 linkuse as main transcript	c.431C>T	p.Ala144Val	missense_variant	4/20	1	NM_005146.5	ENSP00000310448	P1	O43290-1
SART1	ENST00000528573.1 linkuse as main transcript	n.551C>T		non_coding_transcript_exon_variant	4/4	4
SART1	ENST00000529532.5 linkuse as main transcript	n.525C>T		non_coding_transcript_exon_variant	4/9	2
SART1	ENST00000530251.1 linkuse as main transcript	c.472C>T	p.Arg158Trp	missense_variant, NMD_transcript_variant	4/5	5		ENSP00000436218

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000599

AC:

AN:

217144

Hom.:

AF XY:

0.0000418

AC XY:

AN XY:

119502

show subpopulations

Gnomad AFR exome

AF:

0.000404

Gnomad AMR exome

AF:

0.0000803

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000156

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000984

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000415

AC:

AN:

1421156

Hom.:

Cov.:

AF XY:

0.0000411

AC XY:

AN XY:

705016

show subpopulations

Gnomad4 AFR exome

AF:

0.000900

Gnomad4 AMR exome

AF:

0.0000590

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000135

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000100

Gnomad4 OTH exome

AF:

0.000120

GnomAD4 genome

AF:

0.000236

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000702

Hom.:

Bravo

AF:

0.000242

ESP6500AA

AF:

0.000456

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.431C>T (p.A144V) alteration is located in exon 4 (coding exon 4) of the SART1 gene. This alteration results from a C to T substitution at nucleotide position 431, causing the alanine (A) at amino acid position 144 to be replaced by a valine (V). 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

Benign

0.081

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.017

Eigen

Benign

-0.049

Eigen_PC

Benign

0.030

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.84

M_CAP

Benign

0.0088

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

MutationTaster

Benign

0.91

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.4

REVEL

Benign

0.046

Sift

Benign

0.28

Sift4G

Benign

0.25

Polyphen

0.29

Vest4

0.14

MVP

0.35

MPC

0.27

ClinPred

0.023

GERP RS

3.4

Varity_R

0.064

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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