rs781416046

Variant names:

• chr19-12930743-C-G
• NM_004461.3:c.154G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-12930743-C-G
• chr19-12930743-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004461.3(FARSA):​c.154G>C​(p.Glu52Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: FARSA NM_004461.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97

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-AS1 (HGNC:50479): (FARSA antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18380404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FARSA	NM_004461.3	c.154G>C	p.Glu52Gln	missense_variant	Exon 2 of 13	ENST00000314606.9	NP_004452.1
FARSA-AS1	NR_149078.1	n.25+197C>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FARSA	ENST00000314606.9	c.154G>C	p.Glu52Gln	missense_variant	Exon 2 of 13	1	NM_004461.3	ENSP00000320309.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1455224 Hom.: 0 Cov.: 32 AF XY: 0.00000414 AC XY: 3 AN XY: 724208

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T;.;T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.036
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.83	T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.6	.;L;L;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.38	.;N;N;.
REVEL	Benign	0.040
Sift	Benign	0.39	.;T;T;.
Sift4G	Benign	0.49	T;T;T;.
Polyphen		0.0050	.;.;B;.
Vest4		0.24
MutPred		0.36		.;Loss of sheet (P = 0.0037);Loss of sheet (P = 0.0037);Loss of sheet (P = 0.0037);
MVP		0.77
MPC		0.38
ClinPred		0.43	T
GERP RS		4.4
Varity_R		0.27
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-13041557;