Genetic Variant FARSA:p.Ala378Ala (chr19-12924700-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004461.3(FARSA):c.1134G>A(p.Ala378Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000279 in 1,592,676 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 2 hom. )

Consequence

FARSA
NM_004461.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.12

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

Rajab interstitial lung disease with brain calcifications 2
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

FARSA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 19-12924700-C-T is Benign according to our data. Variant chr19-12924700-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2649357.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.12 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004461.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARSA	NM_004461.3	MANE Select	c.1134G>A	p.Ala378Ala	synonymous	Exon 10 of 13	NP_004452.1	Q9Y285-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FARSA	ENST00000314606.9	TSL:1 MANE Select	c.1134G>A	p.Ala378Ala	synonymous	Exon 10 of 13	ENSP00000320309.3	Q9Y285-1
FARSA	ENST00000588025.5	TSL:5	c.1254G>A	p.Ala418Ala	synonymous	Exon 11 of 14	ENSP00000468051.1	K7ER00
FARSA	ENST00000941155.1		c.1068G>A	p.Ala356Ala	synonymous	Exon 10 of 13	ENSP00000611214.1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000647

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000274

AC:

AN:

237462

AF XY:

0.000275

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.0000894

Gnomad ASJ exome

AF:

0.000238

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000485

Gnomad NFE exome

AF:

0.000541

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000276

AC:

397

AN:

1440482

Hom.:

Cov.:

AF XY:

0.000315

AC XY:

225

AN XY:

713220

show subpopulations

African (AFR)

AF:

0.0000903

AC:

AN:

33208

American (AMR)

AF:

0.0000687

AC:

AN:

43688

Ashkenazi Jewish (ASJ)

AF:

0.000122

AC:

AN:

24638

East Asian (EAS)

AF:

0.00

AC:

AN:

39398

South Asian (SAS)

AF:

0.0000240

AC:

AN:

83330

European-Finnish (FIN)

AF:

0.0000760

AC:

AN:

52658

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.000341

AC:

375

AN:

1098502

Other (OTH)

AF:

0.000118

AC:

AN:

59382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

102

127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000309

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41448

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000647

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000663

Hom.:

Bravo

AF:

0.000276

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.4

(source)

DANN

Benign

0.88

PhyloP100

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over