Variant 19-12924708-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_004461.3(FARSA):c.1126G>T(p.Val376Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00173 in 1,595,294 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0037 ( 14 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 33 hom. )

Consequence

FARSA
NM_004461.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.65

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0105448365).

BP6

Variant 19-12924708-C-A is Benign according to our data. Variant chr19-12924708-C-A is described in ClinVar as [Benign]. Clinvar id is 3034463.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00372 (566/152328) while in subpopulation EAS AF= 0.0263 (136/5178). AF 95% confidence interval is 0.024. There are 14 homozygotes in gnomad4. There are 346 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FARSA	NM_004461.3 linkuse as main transcript	c.1126G>T	p.Val376Leu	missense_variant	10/13	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.1126G>T	p.Val376Leu	missense_variant	10/13	1	NM_004461.3	ENSP00000320309	P1	Q9Y285-1

Frequencies

GnomAD3 genomes

AF:

0.00373

AC:

567

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0264

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00662

AC:

1589

AN:

240094

Hom.:

AF XY:

0.00557

AC XY:

720

AN XY:

129196

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.0283

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0315

Gnomad SAS exome

AF:

0.000923

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000277

Gnomad OTH exome

AF:

0.00360

GnomAD4 exome

AF:

0.00153

AC:

2201

AN:

1442966

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

1004

AN XY:

714880

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.0259

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0217

Gnomad4 SAS exome

AF:

0.000810

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000246

Gnomad4 OTH exome

AF:

0.00190

GnomAD4 genome

AF:

0.00372

AC:

566

AN:

152328

Hom.:

Cov.:

AF XY:

0.00465

AC XY:

346

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.0261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0263

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000991

Hom.:

Bravo

AF:

0.00467

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00504

AC:

612

Asia WGS

AF:

0.0120

AC:

AN:

3478

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

Feb 28, 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

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.033

T;.;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.98

D;D;D

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.59

.;.;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.3

.;N;N

REVEL

Benign

0.23

Sift

Benign

0.29

.;T;T

Sift4G

Benign

0.41

T;T;T

Polyphen

0.079

.;.;B

Vest4

0.50

MutPred

0.48

.;.;Gain of sheet (P = 0.0827);

MVP

0.63

MPC

0.50

ClinPred

0.028

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.50

gMVP

0.68

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