NM_004461.3:c.503+390C>T

Variant names:

• chr19-12929833-G-A
• rs2967890
• NM_004461.3:c.503+390C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004461.3(FARSA):​c.503+390C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 152,110 control chromosomes in the GnomAD database, including 51,567 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.

• Frequency: Genomes: 𝑓 0.82 (51567 hom., cov: 31)
• Consequence: FARSA NM_004461.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• Publications: 16 publications found

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]

FARSA Gene-Disease associations (from GenCC):

• Rajab interstitial lung disease with brain calcifications 2

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004461.3. 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
	FARSA	NM_004461.3	MANE Select	c.503+390C>T		intron	N/A	NP_004452.1	Q9Y285-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARSA	ENST00000314606.9	TSL:1 MANE Select	c.503+390C>T		intron	N/A	ENSP00000320309.3	Q9Y285-1
	FARSA	ENST00000592662.5	TSL:1	n.505+390C>T		intron	N/A
	FARSA	ENST00000588025.5	TSL:5	c.623+390C>T		intron	N/A	ENSP00000468051.1	K7ER00

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124661 AN: 151992 Hom.: 51520 Cov.: 31

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.791

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.820 AC: 124756 AN: 152110 Hom.: 51567 Cov.: 31 AF XY: 0.823 AC XY: 61174 AN XY: 74348

African (AFR) AF: 0.908 AC: 37687 AN: 41520

American (AMR) AF: 0.768 AC: 11713 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2825 AN: 3472

East Asian (EAS) AF: 0.945 AC: 4873 AN: 5158

South Asian (SAS) AF: 0.827 AC: 3986 AN: 4820

European-Finnish (FIN) AF: 0.814 AC: 8614 AN: 10580

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52559 AN: 67994

Other (OTH) AF: 0.784 AC: 1655 AN: 2110

Alfa AF: 0.788 Hom.: 138822

Bravo AF: 0.817

Asia WGS AF: 0.854 AC: 2971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.81
DANN	Benign	0.38
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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: rs2967890; hg19: chr19-13040647;