NM_004461.3:c.841+1422C>T

Variant names:

• chr19-12926920-G-A
• rs62109865
• NM_004461.3:c.841+1422C>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.841+1422C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0482 in 152,308 control chromosomes in the GnomAD database, including 234 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 0.048 (234 hom., cov: 32)
• Consequence: FARSA NM_004461.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0679 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.841+1422C>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.841+1422C>T		intron	N/A	ENSP00000320309.3	Q9Y285-1
	FARSA	ENST00000588025.5	TSL:5	c.961+1422C>T		intron	N/A	ENSP00000468051.1	K7ER00
	FARSA	ENST00000941155.1		c.775+1422C>T		intron	N/A	ENSP00000611214.1

Frequencies

GnomAD3 genomes AF: 0.0482 AC: 7343 AN: 152190 Hom.: 234 Cov.: 32

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0420

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0656

Gnomad FIN AF: 0.0602

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0696

Gnomad OTH AF: 0.0593

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

GnomAD4 genome AF: 0.0482 AC: 7337 AN: 152308 Hom.: 234 Cov.: 32 AF XY: 0.0481 AC XY: 3582 AN XY: 74476

African (AFR) AF: 0.0129 AC: 537 AN: 41588

American (AMR) AF: 0.0419 AC: 641 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0660 AC: 229 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.0658 AC: 318 AN: 4830

European-Finnish (FIN) AF: 0.0602 AC: 639 AN: 10608

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0696 AC: 4734 AN: 68016

Other (OTH) AF: 0.0582 AC: 123 AN: 2114

Alfa AF: 0.0502 Hom.: 145

Bravo AF: 0.0459

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.70
DANN	Benign	0.29
PhyloP100		-0.39
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: rs62109865; hg19: chr19-13037734;