Variant 12-108526396-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_014706.4(SART3):c.2073C>T(p.Asp691=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 1,614,098 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 51 hom. )

Consequence

SART3
NM_014706.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0850

Variant links:

Genes affected

SART3 (HGNC:16860): (spliceosome associated factor 3, U4/U6 recycling protein) The protein encoded by this gene is an RNA-binding nuclear protein that is a tumor-rejection antigen. This antigen possesses tumor epitopes capable of inducing HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes in cancer patients and may be useful for specific immunotherapy. This gene product is found to be an important cellular factor for HIV-1 gene expression and viral replication. It also associates transiently with U6 and U4/U6 snRNPs during the recycling phase of the spliceosome cycle. This encoded protein is thought to be involved in the regulation of mRNA splicing. [provided by RefSeq, Jul 2008]

SART3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 12-108526396-G-A is Benign according to our data. Variant chr12-108526396-G-A is described in ClinVar as [Benign]. Clinvar id is 788887.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.085 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00427 (6243/1461776) while in subpopulation MID AF= 0.0194 (112/5768). AF 95% confidence interval is 0.0165. There are 51 homozygotes in gnomad4_exome. There are 3504 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd at 561 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SART3	NM_014706.4 linkuse as main transcript	c.2073C>T	p.Asp691=	synonymous_variant	16/19	ENST00000546815.6
SART3	NM_001410983.1 linkuse as main transcript	c.2127C>T	p.Asp709=	synonymous_variant	16/19
SART3	XM_047429916.1 linkuse as main transcript	c.1209C>T	p.Asp403=	synonymous_variant	11/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SART3	ENST00000546815.6 linkuse as main transcript	c.2073C>T	p.Asp691=	synonymous_variant	16/19	5	NM_014706.4	P1	Q15020-1

Frequencies

GnomAD3 genomes

AF:

0.00369

AC:

561

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0151

Gnomad FIN

AF:

0.00932

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00348

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00572

AC:

1439

AN:

251424

Hom.:

AF XY:

0.00657

AC XY:

893

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.0205

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0169

Gnomad FIN exome

AF:

0.00999

Gnomad NFE exome

AF:

0.00353

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00427

AC:

6243

AN:

1461776

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

3504

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.0225

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0165

Gnomad4 FIN exome

AF:

0.00824

Gnomad4 NFE exome

AF:

0.00294

Gnomad4 OTH exome

AF:

0.00525

GnomAD4 genome

AF:

0.00367

AC:

559

AN:

152322

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

313

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0149

Gnomad4 FIN

AF:

0.00932

Gnomad4 NFE

AF:

0.00347

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00466

Hom.:

Bravo

AF:

0.00292

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.00447

EpiControl

AF:

0.00450

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

Cadd

Benign

1.4

Dann

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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