Variant 19-12924192-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_004461.3(FARSA):c.1347C>T(p.Pro449=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,613,960 control chromosomes in the GnomAD database, including 10,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.088 ( 770 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9852 hom. )

Consequence

FARSA
NM_004461.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -5.10

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 19-12924192-G-A is Benign according to our data. Variant chr19-12924192-G-A is described in ClinVar as [Benign]. Clinvar id is 3055967.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-5.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FARSA	NM_004461.3 linkuse as main transcript	c.1347C>T	p.Pro449=	synonymous_variant	12/13	ENST00000314606.9	NP_004452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FARSA	ENST00000314606.9 linkuse as main transcript	c.1347C>T	p.Pro449=	synonymous_variant	12/13	1	NM_004461.3	ENSP00000320309	P1	Q9Y285-1

Frequencies

GnomAD3 genomes

AF:

0.0879

AC:

13366

AN:

152100

Hom.:

764

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0230

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.0833

Gnomad EAS

AF:

0.0999

Gnomad SAS

AF:

0.0775

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.0834

GnomAD3 exomes

AF:

0.109

AC:

27281

AN:

251340

Hom.:

1647

AF XY:

0.107

AC XY:

14512

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.0217

Gnomad AMR exome

AF:

0.151

Gnomad ASJ exome

AF:

0.0841

Gnomad EAS exome

AF:

0.0962

Gnomad SAS exome

AF:

0.0784

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.113

AC:

164816

AN:

1461742

Hom.:

9852

Cov.:

AF XY:

0.112

AC XY:

81334

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.0185

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.0844

Gnomad4 EAS exome

AF:

0.0892

Gnomad4 SAS exome

AF:

0.0786

Gnomad4 FIN exome

AF:

0.112

Gnomad4 NFE exome

AF:

0.119

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.0879

AC:

13380

AN:

152218

Hom.:

770

Cov.:

AF XY:

0.0876

AC XY:

6516

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0229

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.0833

Gnomad4 EAS

AF:

0.100

Gnomad4 SAS

AF:

0.0777

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.123

Gnomad4 OTH

AF:

0.0821

Alfa

AF:

0.110

Hom.:

1454

Bravo

AF:

0.0868

Asia WGS

AF:

0.0910

AC:

319

AN:

3478

EpiCase

AF:

0.118

EpiControl

AF:

0.106

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FARSA-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 19, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.30

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over