19-12925074-G-GT

Position:

• chr19-12925074-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004461.3(FARSA):​c.926+15_926+16insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00679 in 1,613,206 control chromosomes in the GnomAD database, including 694 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (360 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (334 hom.)
• Consequence: FARSA NM_004461.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.04

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 19-12925074-G-GT is Benign according to our data. Variant chr19-12925074-G-GT is described in ClinVar as [Benign]. Clinvar id is 1250447.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FARSA	NM_004461.3	c.926+15_926+16insA		intron_variant		ENST00000314606.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARSA	ENST00000314606.9	c.926+15_926+16insA		intron_variant		1	NM_004461.3	P1

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 5554 AN: 152116 Hom.: 360 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0248

GnomAD3 exomes AF: 0.00935 AC: 2330 AN: 249316 Hom.: 137 AF XY: 0.00692 AC XY: 935 AN XY: 135018

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.00488

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000196

Gnomad OTH exome AF: 0.00361

GnomAD4 exome AF: 0.00370 AC: 5407 AN: 1460972 Hom.: 334 Cov.: 33 AF XY: 0.00317 AC XY: 2306 AN XY: 726764

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.00611

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000123

Gnomad4 OTH exome AF: 0.00796

GnomAD4 genome AF: 0.0365 AC: 5552 AN: 152234 Hom.: 360 Cov.: 32 AF XY: 0.0356 AC XY: 2648 AN XY: 74430

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.00153 Hom.: 5

Bravo AF: 0.0416

Asia WGS AF: 0.00722 AC: 26 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs113375740; hg19: chr19-13035888;