12-108523553-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_014706.4(SART3):c.2796C>T(p.Asn932=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,614,024 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (45 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (42 hom.)
• Consequence: SART3 NM_014706.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.71

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]

FICD (HGNC:18416): (FIC domain protein adenylyltransferase) Enables several functions, including ATP binding activity; Hsp70 protein binding activity; and chaperone binding activity. Involved in protein adenylylation; regulation of IRE1-mediated unfolded protein response; and response to endoplasmic reticulum stress. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 12-108523553-G-A is Benign according to our data. Variant chr12-108523553-G-A is described in ClinVar as [Benign]. Clinvar id is 785423.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.71 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0138 (2101/152246) while in subpopulation AFR AF= 0.0446 (1854/41544). AF 95% confidence interval is 0.0429. There are 45 homozygotes in gnomad4. There are 992 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 2098 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SART3	NM_014706.4	c.2796C>T	p.Asn932=	synonymous_variant	19/19	ENST00000546815.6
SART3	NM_001410983.1	c.2850C>T	p.Asn950=	synonymous_variant	19/19
SART3	XM_047429916.1	c.1932C>T	p.Asn644=	synonymous_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SART3	ENST00000546815.6	c.2796C>T	p.Asn932=	synonymous_variant	19/19	5	NM_014706.4	P1

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2098 AN: 152128 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.0447

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00923

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000764

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00446 AC: 1120 AN: 251298 Hom.: 23 AF XY: 0.00350 AC XY: 475 AN XY: 135862

Gnomad AFR exome AF: 0.0467

Gnomad AMR exome AF: 0.00497

Gnomad ASJ exome AF: 0.00695

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000713

Gnomad OTH exome AF: 0.00554

GnomAD4 exome AF: 0.00202 AC: 2949 AN: 1461778 Hom.: 42 Cov.: 31 AF XY: 0.00192 AC XY: 1398 AN XY: 727202

Gnomad4 AFR exome AF: 0.0476

Gnomad4 AMR exome AF: 0.00563

Gnomad4 ASJ exome AF: 0.00616

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000549

Gnomad4 OTH exome AF: 0.00449

GnomAD4 genome AF: 0.0138 AC: 2101 AN: 152246 Hom.: 45 Cov.: 32 AF XY: 0.0133 AC XY: 992 AN XY: 74444

Gnomad4 AFR AF: 0.0446

Gnomad4 AMR AF: 0.00922

Gnomad4 ASJ AF: 0.00721

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000765

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00683 Hom.: 2

Bravo AF: 0.0161

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.00136

EpiControl AF: 0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	-0.69
Cadd	Benign	0.34
Dann	Benign	0.91
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

Other links and lift over

dbSNP: rs34709181; hg19: chr12-108917330;