Variant chr19-12924926-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004461.3(FARSA):c.1004C>T(p.Ala335Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,614,236 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: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

FARSA
NM_004461.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.13

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:

FARSA (HGNC:):

FARSA links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30571237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FARSA	NM_004461.3 linkuse as main transcript	c.1004C>T	p.Ala335Val	missense_variant	9/13	ENST00000314606.9	NP_004452.1	Q9Y285-1Q6IBR2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FARSA	ENST00000314606.9 linkuse as main transcript	c.1004C>T	p.Ala335Val	missense_variant	9/13	1	NM_004461.3	ENSP00000320309.3		Q9Y285-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251426

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000459

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2024

The c.1004C>T (p.A335V) alteration is located in exon 9 (coding exon 9) of the FARSA gene. This alteration results from a C to T substitution at nucleotide position 1004, causing the alanine (A) at amino acid position 335 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0063

T;.;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.031

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.17

.;.;N

PrimateAI

Benign

0.35

PROVEAN

Benign

1.4

.;N;N

REVEL

Benign

0.073

Sift

Benign

0.071

.;T;T

Sift4G

Benign

0.12

T;T;T

Polyphen

0.0080

.;.;B

Vest4

0.34

MutPred

0.51

.;.;Loss of disorder (P = 0.0517);

MVP

0.68

MPC

0.39

ClinPred

0.056

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.050

gMVP

0.66

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