rs34709181

Variant names:

• chr12-108523553-G-A
• rs34709181
• NM_014706.4:c.2796C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-108523553-G-A
• chr12-108523553-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014706.4(SART3):​c.2796C>T​(p.Asn932Asn) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.71
• Publications: 2 publications found

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]

FICD Gene-Disease associations (from GenCC):

• spastic paraplegia 92, autosomal recessive

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 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 VariationId is 785423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 45 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014706.4. 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
	SART3	NM_014706.4	MANE Select	c.2796C>T	p.Asn932Asn	synonymous	Exon 19 of 19	NP_055521.1	Q15020-1
	SART3	NM_001410983.1		c.2850C>T	p.Asn950Asn	synonymous	Exon 19 of 19	NP_001397912.1	A0A499FI31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SART3	ENST00000546815.6	TSL:5 MANE Select	c.2796C>T	p.Asn932Asn	synonymous	Exon 19 of 19	ENSP00000449386.2	Q15020-1
	SART3	ENST00000228284.8	TSL:1	c.2850C>T	p.Asn950Asn	synonymous	Exon 19 of 19	ENSP00000228284.4	A0A499FI31
	SART3	ENST00000431469.6	TSL:1	c.2688C>T	p.Asn896Asn	synonymous	Exon 18 of 18	ENSP00000414453.2	Q15020-4

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

GnomAD2 exomes AF: 0.00446 AC: 1120 AN: 251298 AF XY: 0.00350

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 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

African (AFR) AF: 0.0476 AC: 1595 AN: 33478

American (AMR) AF: 0.00563 AC: 252 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00616 AC: 161 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86252

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53394

Middle Eastern (MID) AF: 0.00841 AC: 48 AN: 5708

European-Non Finnish (NFE) AF: 0.000549 AC: 611 AN: 1111996

Other (OTH) AF: 0.00449 AC: 271 AN: 60390

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

African (AFR) AF: 0.0446 AC: 1854 AN: 41544

American (AMR) AF: 0.00922 AC: 141 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00721 AC: 25 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000765 AC: 52 AN: 68012

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.00718 Hom.: 3

Bravo AF: 0.0161

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.00136

EpiControl AF: 0.000771

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.34
DANN	Benign	0.91
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs34709181; hg19: chr12-108917330;