rs2293683

Positions:

• chr19-12928470-A-G
• chr19-12928470-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004461.3(FARSA):​c.726-13T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,613,602 control chromosomes in the GnomAD database, including 339,392 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.64 (31673 hom., cov: 31)
  • Exomes 𝑓: 0.65 (307719 hom.)
• Consequence: FARSA NM_004461.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

Genes affected

FARSA (HGNC:3592): (phenylalanyl-tRNA synthetase subunit alpha) Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. This gene encodes a product which is similar to the catalytic subunit of prokaryotic and Saccharomyces cerevisiae phenylalanyl-tRNA synthetases (PheRS). This gene product has been shown to be expressed in a tumor-selective and cell cycle stage- and differentiation-dependent manner, the first member of the tRNA synthetase gene family shown to exhibit this type of regulated expression [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FARSA	NM_004461.3	c.726-13T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000314606.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARSA	ENST00000314606.9	c.726-13T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004461.3	P1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97573 AN: 151844 Hom.: 31646 Cov.: 31

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.643

GnomAD3 exomes AF: 0.654 AC: 164302 AN: 251044 Hom.: 54673 AF XY: 0.661 AC XY: 89734 AN XY: 135690

Gnomad AFR exome AF: 0.611

Gnomad AMR exome AF: 0.524

Gnomad ASJ exome AF: 0.724

Gnomad EAS exome AF: 0.820

Gnomad SAS exome AF: 0.725

Gnomad FIN exome AF: 0.703

Gnomad NFE exome AF: 0.639

Gnomad OTH exome AF: 0.659

GnomAD4 exome AF: 0.646 AC: 944432 AN: 1461640 Hom.: 307719 Cov.: 51 AF XY: 0.650 AC XY: 472570 AN XY: 727112

Gnomad4 AFR exome AF: 0.619

Gnomad4 AMR exome AF: 0.532

Gnomad4 ASJ exome AF: 0.727

Gnomad4 EAS exome AF: 0.839

Gnomad4 SAS exome AF: 0.720

Gnomad4 FIN exome AF: 0.697

Gnomad4 NFE exome AF: 0.634

Gnomad4 OTH exome AF: 0.659

GnomAD4 genome AF: 0.643 AC: 97641 AN: 151962 Hom.: 31673 Cov.: 31 AF XY: 0.647 AC XY: 47996 AN XY: 74234

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.724

Gnomad4 EAS AF: 0.818

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.639

Gnomad4 OTH AF: 0.639

Alfa AF: 0.645 Hom.: 61570

Bravo AF: 0.630

Asia WGS AF: 0.727 AC: 2527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.067
DANN	Benign	0.35
BranchPoint Hunter		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2293683; hg19: chr19-13039284;