rs35087277

Variant names:

• chr19-12924908-T-A
• rs35087277
• NM_004461.3:c.1022A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-12924908-T-A
• chr19-12924908-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004461.3(FARSA):​c.1022A>T​(p.Gln341Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q341R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FARSA NM_004461.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.91

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FARSA	NM_004461.3	c.1022A>T	p.Gln341Leu	missense_variant	Exon 9 of 13	ENST00000314606.9	NP_004452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FARSA	ENST00000314606.9	c.1022A>T	p.Gln341Leu	missense_variant	Exon 9 of 13	1	NM_004461.3	ENSP00000320309.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	0.97
DEOGEN2	Benign	0.10	T;.;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.50	T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.9	.;.;M
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.6	.;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.018	.;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		0.010	.;.;B
Vest4		0.50
MutPred		0.44		.;.;Loss of methylation at K342 (P = 0.0421);
MVP		0.79
MPC		0.39
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.39
gMVP		0.70

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: rs35087277; hg19: chr19-13035722;