Genetic Variant NM_005146.5:c.271C>T (chr11-65962051-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005146.5(SART1):c.271C>T(p.Arg91Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00006 in 1,284,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

SART1
NM_005146.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41

Publications

0 publications found

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24597886).

BS2

High AC in GnomAd4 at 9 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SART1	NM_005146.5	MANE Select	c.271C>T	p.Arg91Trp	missense	Exon 1 of 20	NP_005137.1	O43290-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SART1	ENST00000312397.10	TSL:1 MANE Select	c.271C>T	p.Arg91Trp	missense	Exon 1 of 20	ENSP00000310448.5	O43290-1
SART1	ENST00000532333.5	TSL:1	n.324C>T		non_coding_transcript_exon	Exon 1 of 2
SART1	ENST00000972145.1		c.271C>T	p.Arg91Trp	missense	Exon 1 of 19	ENSP00000642204.1

Frequencies

GnomAD3 genomes

AF:

0.0000663

AC:

AN:

135650

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000139

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000225

AC:

AN:

88898

AF XY:

0.0000396

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000641

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000592

AC:

AN:

1148748

Hom.:

Cov.:

AF XY:

0.0000638

AC XY:

AN XY:

564048

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21456

American (AMR)

AF:

0.00

AC:

AN:

24452

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16400

East Asian (EAS)

AF:

0.00

AC:

AN:

11384

South Asian (SAS)

AF:

0.00

AC:

AN:

73462

European-Finnish (FIN)

AF:

0.0000499

AC:

AN:

20038

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2954

European-Non Finnish (NFE)

AF:

0.0000716

AC:

AN:

935568

Other (OTH)

AF:

0.00

AC:

AN:

43034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.0000663

AC:

AN:

135650

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

64572

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

36824

American (AMR)

AF:

0.00

AC:

AN:

12024

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3338

East Asian (EAS)

AF:

0.00

AC:

AN:

4168

South Asian (SAS)

AF:

0.00

AC:

AN:

4038

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.000139

AC:

AN:

64654

Other (OTH)

AF:

0.00

AC:

AN:

1902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.000324

Hom.:

Bravo

AF:

0.0000491

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.027

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

1.4

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.15

Sift

Uncertain

0.023

Sift4G

Uncertain

0.017

Polyphen

1.0

Vest4

0.21

MVP

0.50

MPC

2.4

ClinPred

0.94

GERP RS

-0.0055

PromoterAI

-0.0020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.31

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over